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 Table of Contents  
ORIGINAL ARTICLE
Year : 2019  |  Volume : 26  |  Issue : 1  |  Page : 18-24

Medication adherence and 24-h blood pressure in apparently uncontrolled hypertensive Nigerian patients


1 Department of Medicine, University of Ibadan, badan, Nigeria
2 Department of Community Medicine, University of Ibadan, badan, Nigeria
3 Department of Medicine, University College Hospital, Ibadan, Nigeria

Date of Web Publication12-Mar-2019

Correspondence Address:
Abiodun Moshood Adeoye
Department of Medicine, College of Medicine, University of Ibadan, Ibadan
Nigeria
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/npmj.npmj_147_18

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  Abstract 

Background: Uncontrolled hypertension is a major risk for major cardiovascular events. While medication adherence determines blood pressure (BP) control, studies on treatment adherence among apparently uncontrolled hypertensives are sorely lacking in sub-Saharan Africa. We report the pattern and correlate of medication adherence among the uncontrolled hypertensive population. Materials and Methods: We investigated 148 age- and sex-matched hypertensive adults on anti-hypertensive medication for a minimum of 1 year. Apparent uncontrolled BP was defined as clinic BP ≥140/90 mmHg, whereas 24-h ambulatory BP monitoring was used to determine the true uncontrolled hypertension and other BP phenotypes. Using the 8-item Morisky medication adherence scale participants were classified into high, moderate and low adherence while Modified Morisky Scale was used to assess knowledge and motivation. Results: The mean age and BP were 61 ± 13.3 years and 158/91 mmHg, respectively. High adherence was found in 4.1% of the participants while 68.9% and 27% had moderate and low adherence, respectively. A third had true uncontrolled hypertension. A high proportion of the study participants also had a high motivation (68.9%) and knowledge (89.2%). Medication adherence was associated with motivation (P = 0.0001), knowledge (P = 0.002) and obesity (P = 0.036). Knowledge was an independent determinant of medication adherence with no significant effect on BP control. Conclusion: High medication adherence was low and a third had true uncontrolled hypertension. Knowledge was an independent predictor of medication adherence with no significant effect on blood control. High medication adherence rather than moderate adherence, and knowledge are indeed needed for adequate BP control.

Keywords: 24 h ambulatory blood pressure, hypertension, medication adherence


How to cite this article:
Adeoye AM, Adebiyi AO, Adebayo OM, Owolabi MO. Medication adherence and 24-h blood pressure in apparently uncontrolled hypertensive Nigerian patients. Niger Postgrad Med J 2019;26:18-24

How to cite this URL:
Adeoye AM, Adebiyi AO, Adebayo OM, Owolabi MO. Medication adherence and 24-h blood pressure in apparently uncontrolled hypertensive Nigerian patients. Niger Postgrad Med J [serial online] 2019 [cited 2019 May 23];26:18-24. Available from: http://www.npmj.org/text.asp?2019/26/1/18/253973


  Introduction Top


Hypertension is the most common cardiovascular disease (CVD) accounting for about 9.4 million deaths per year worldwide.[1] Increased blood pressure (BP) has been estimated by the Global Burden of Disease study to be the leading risk factor for disability-adjusted life years worldwide and the trend is predicted to worsen over years.[2],[3] The World Health Organisation data in 2005 have suggested that uncontrolled BP triples the risk of coronary artery disease and speeds up the progression of diabetic nephropathy, retinopathy and neuropathy.[4]

Despite increased global awareness of BP, the rate of BP control is still poor and varies globally. Data from the National Health and Nutrition Examination Survey (NHANES, United States) showed that the prevalence of controlled hypertension among adults rose from 31.6% in 1999–2000 to 53.1% in 2009–2010 which is clearly below the goal of 61.2% by 2020.[5] Compared with older adults, young adults had a lower prevalence of awareness, treatment and control of hypertension. Women were more likely treating their hypertension and had it under control.

Uncontrolled hypertension is a major medical concern in developing countries such as Sub-Saharan African (SSA) as much as it is in developed countries.[6] In SSA, only 7% of the hypertensive population had controlled BP.[7] Despite the lack of consensus on the latest guidelines, using a target BP of 130/80 mmHg for BP control instead of 140/90 mmHg shows that uncontrolled hypertension may be higher in SSA than been currently observed.[8],[9] Ambulatory BP monitoring (ABPM) is a useful tool in ascertaining the true uncontrolled hypertension, but such data are lacking in SSA. Previous studies analysed in the systematic review used clinic BP measurement making an assessment of the true prevalence of uncontrolled hypertension in Africa inconclusive.

Poor medication adherence had been shown as a harbinger for increasing incidences and prevalence of uncontrolled hypertension. Several factors have been associated with poor drug compliance in hypertension, such as the chronicity of the diseases, duration and number of pills as well as other co-morbidities. A study had shown that compared with Asians, nearly two-thirds of the African population were non-adherent and 83.7% of uncontrolled BP patients were non-adherent to medications.[10] Failure to achieve BP goals is associated with increased risk of target organ damage; hence, the need to identify modifiable factors that determines medication adherence to antihypertensive.[11] Despite the high rate of uncontrolled hypertension in SSA, data on the contribution of drug adherence to this observed trend are generally lacking. This study, therefore, documents the pattern and determinants of medication adherence among the uncontrolled hypertensive adult patients in South Western Nigeria comparing clinic and ambulatory BP measurements with the view to define the true uncontrolled hypertension and facilitate the deployment of appropriate strategies for the management of hypertension.


  Materials and Methods Top


Subjects and methods

This cross-sectional and comparative study was conducted over a period of 1 year from July 2014 to June 2015 following approval by the Joint University of Ibadan/University College Hospital Ethics Committee, Ibadan, Nigeria with approval reference number UI/EC/14/0136 dated 19th June 2014 and renewed on the 17th August 2015.

Sample size and power justification

Averagely, 30 new hypertensive patients attend the cardiology division, medical out-patient Department of University College Hospital weekly and approximately 30% of the patients have controlled BP (i.e., 468 patients with uncontrolled BP per year).[12],[13] A previous study showed that 83.7% of uncontrolled BP patients in Africa were non-adherent to medications.[10] Given the finite population of patients with uncontrolled BP per year, a minimum sample size of 97 from a population of 500 will achieve 90.5% power to detect a minimal 5% difference using a two-sided exact test with a target significance level of 0.05. Consequently, consecutive 148 hypertensive adults (77 women and 71 men) on anti-hypertensive medications for a minimum of 1 year with clinic/office BP ≥140/90 mmHg who are attending cardiology division, medical out-patient department of University College Hospital were included in the present study. Informed consent was obtained from all participants.

Pre-tested questionnaires were administered on all the participants to obtain information on demographics, family history of CVDs, lifestyles, duration of hypertension and medication history detailing the number of pills and types of anti-hypertensives. Clinic (office) BP was measured using a standard Omron (HEM711DLX) BP apparatus on the left arm placed at heart level after 5-min rest and using appropriate cuff size with the subject in the sitting with back rested and legs uncrossed. The average of last two out of three BP measurements obtained with a minimum of 1 min apart was used in the present analysis. As demonstrated in a study the sensitivity and specificity of the Omron apparatus to detect hypertension were 88.2% and 98.6%, respectively.[14]

Anthropometric measurements were obtained. Height was measured barefooted to the nearest centimetre using a ruler attached to the wall, while weight was measured to the nearest 0.1 kg using an electronic scale with the subject wearing a light dress. Waist circumference measurements were taken at the end of expiration midway between the rib cage and the iliac crest using an anthropometric measuring tape. Average of three measured waist circumferences, recorded to the nearest tenth of a centimetre was obtained for analysis.

All the participants had a 24-h ABPM done using SpaceLabs ABPM (SpaceLabs Healthcare, Issaquah, WA, USA) which was placed on the non-dominant arm. Cuff sizes were selected after measuring participants' non-dominant arm circumference. The machine was programmed to read half hourly from 7 a.m. to 10 p.m. and hourly from 10 p.m. to 7 a.m. Measurements were done during weekdays to allow participants to return to the hospital after 24 h for disconnection of the ABPM monitoring machine. Patients were encouraged to proceed with their routine daily activities but to avoid vigorous physical activities and keep motionless at the time of measurement. After 24 h of monitoring, participants returned to our centre to have the device removed. For an ABPM measurement to be considered complete, a participant was required to have at least 10 daytime and 5 night-time systolic BP (SBP) and diastolic BP (DBP) measurements.

Medication adherence assessment

The 8-item Morisky Medication Adherence Scale (MMAS-8) was used to study the attitude of the participants to anti-hypertensive drug adherence in addition to knowledge of the importance of medication and motivation for medication compliance. MMAS-8 is an 8-item self-reported adherence measure pretested 8 points written in English and interpreted into local languages by trained research assistant fluent in the language as and when needed.[15],[16] The following questions were used: Do you ever forget to take your medication? Are you sometimes careless about the time you take your medication? When you feel better, do you sometimes stop taking the medication?; When you feel bad due to the medication, do you sometimes stop taking it? Patients were considered high adherent when answered 'no' to all questions. Adherence was considered to be moderate when the patient responded affirmatively to one or two of the four questions of this questionnaire. Modified Morisky Scale (MMS) was used to assess motivation and knowledge by answering 'Yes (0)' or 'No (1)' to the following questions except item 5 where 'Yes' (1) of 'No (0)'. Motivation: Do you ever forget to take your medicine? Are you careless at times about taking your medicine? Sometimes do you forget to refill your prescription medicine on time? With a score of 0–1 as low motivation and 2–3 as high motivation. Knowledge: When you feel better to do you sometimes stop taking your medicine? Sometimes if you feel worse when you take your medicine, do you stop taking it? Do you know the long-term benefit of taking your medicine as told to you by your doctor or pharmacist (Yes [1] or No [0]? With the score of 0–1 as low knowledge and 2–3 high knowledge. In addition to using the test by Morisky et al., we evaluated the number of medications used by the patient through their self-report and medical record verification.[16] The MMAS-8 used, showed a Cronbach's alpha of 0.78 implying high internal consistency and this tool have been validated in the Nigerian population.[17],[18]

Venous blood samples in a fasted state were obtained for lipid profile (total cholesterol, triglycerides, high-density lipoprotein and low-density lipoprotein), creatinine and blood glucose. Serum glucose was measured using glucose oxidase method and lipid profile by enzymatic colorimetric method. Obesity was classified based on BMI in kg/m2 as normal (<25), overweight (25–29.9) and obese (≥30).[19]

Hypertension was defined as SBP ≥140 mmHg and/or DBP ≥90 mmHg or being on antihypertensive treatment. Using clinic/office BP and ABPM, we evaluated three phenotype domains: elevated mean clinic and/or daytime BP, diurnal BP patterns and a disparity between clinic hypertension and out-of-clinic hypertension. Elevated clinic BP was defined as mean clinic SBP ≥140 mm Hg or DBP ≥90 mm Hg; elevated daytime BP as mean daytime SBP ≥135 mm Hg or DBP ≥85 mm Hg; and elevated night-time BP as mean night-time SBP ≥120 mm Hg or DBP ≥70 mm Hg.[20] Diurnal BP patterns included nocturnal hypertension, isolated nocturnal hypertension and a non-dipping BP pattern. Mismatches between clinic Blood pressure and out-of-clinic blood pressure measurements included white coat hypertension, masked hypertension and masked isolated nocturnal hypertension. True uncontrolled hypertension was defined as elevated daytime BP.

Inclusion and exclusion criteria

Participants aged 18 years and above with at least 1-year duration of hypertension on treatment who consented were recruited. Participants were ensured to have been on at least one anti-hypertension drug with BP ≥140/90 mmHg at recruitment and two or three previous clinic visits. Individuals who had kidney transplantation or refused consent were excluded from the study.

Data management

Data were analysed using the Statistical Package for the Social Sciences (SPSS) for Windows version 22.0 (IBM, Armonk, NY, USA). Estimates were expressed as either mean values (±standard deviation) for continuous variables or proportions (percentage) for categorical variables. Comparison of statistical significance was by independent Student's t-test for continuous variables or the Chi-square and one-way ANOVA for categorical variables. Binary logistic regression was fitted to determine the correlates of medication adherence. The significance level was set at P ≤ 0.05.


  Results Top


[Table 1] depicts the baseline characteristics of the study participants and 148 participants with clinic uncontrolled hypertension comprising 52% of women. The mean age and BPs were 61 ± 13.3 years and 158/91 mmHg, respectively. Men had higher mean serum creatinine whereas women had higher total cholesterol and low-density cholesterol. Apart from higher mean daytime DBP and relatively better dipping status among men, other clinic and ambulatory BP parameters were comparable across sex. A third of the participants had true uncontrolled hypertension with a higher mean clinic and ambulatory BP parameters compared with those with apparently uncontrolled hypertension [Table 2]. As shown in [Table 3], only 4.1% had high adherence, whereas 68.9% had moderate adherence, and 27% low adherence. Non-adherers had higher mean 24 h DBP, daytime and nighttime SBP and DBP while clinic BP measurements were comparable. From [Table 4], a high proportion of the study participants also had a high motivation (68.9%) and knowledge (89.2%). Medication adherence was associated with motivation (P = 0.0001), knowledge (P = 0.002) and obesity (P = 0.036) but not with sex, marital status, occupation, education level, family history or duration of hypertension, smoking status, alcohol use, age group and pill number. Nearly 66% had white coat effect whereas 80.5% were non-dippers. No significant association between true uncontrolled hypertension and medication adherence. As shown in [Table 5], knowledge of long-term benefits of hypertension medication use was an independent determinant of medication adherence.
Table 1: Gender-based characteristics of the study population

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Table 2: Characteristics of true uncontrolled hypertension based on ambulatory blood pressure monitoring

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Table 3: Baseline characteristics based on medication adherence

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Table 4: Determinants of medication adherence

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Table 5: Correlates of medication adherence in the study population

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  Discussion Top


In the current study, high medication adherence was low despite the high level of motivation and knowledge of hypertension. Approximately 4 out of 5 participants were non-dippers while a third of the participants had true uncontrolled hypertension. Knowledge of long-term benefits of hypertension medication use was an independent determinant of medication adherence.

The prevalence of treatment adherence varies depending on the study participants, the region and tools for adherence assessment.[16],[21],[22],[23] In several past studies, simple pre-validated self-reported questionnaires were commonly used for medication adherence assessment, especially among the hypertensive populations. In a systematic review of studies that used the Modified Morisky 8-items scale (MMS) as in this study, the global prevalence of medication non-adherence was 45.2% among hypertensive population while 83.7% of uncontrolled hypertensive were non-adherent.[10] This is similar to our findings of 95.9% of apparently uncontrolled hypertensive non-adherent. Using the MMS classification of high, moderate and low adherence our study compared to that of another study in Iran, which found 8.1%, 40.5% and 51.4% patients in high, moderate and low adherence levels, respectively.[24] This is, however, lower than the findings by Grezzana et al. who found 65.7%, 20.3% and 14.7%, respectively, for high, moderate and low adherence, respectively.[25] The discrepancies may result from different study groups; while we studied apparently uncontrolled hypertensive, their study population were heterogeneous involving both controlled and uncontrolled hypertensives. Furthermore, the study population appeared older (61 ± 13.3 vs. 59.8 ± 12.7 years).

Single factor evaluation has failed to predict medication adherence. In this study, greater proportions of adherent and moderately adherent participants had knowledge of hypertension and benefits of long-term use of antihypertensive and were well motivated. The findings of the beneficial effect of knowledge and motivation on medication adherence have not been conclusive; while some found positive relations others did not.[26] Our findings of knowledge as an independent determinant of adherence are similar to the findings among 385 hypertensive patients in Pakistan.[27] Studies have also shown that weight gain or loss affect treatment adherence.[28] In a CARDIA study, obesity was shown to modify the association of race/ethnicity with the relationship of medication adherence.[29] It was observed in the current study that a greater proportion of overweight or obese participants were either moderately adherent or non-adherent with the medication. While the causal relationship could not be established, the concurrence of the two complex lifestyle behaviour is worrisome considering the increasing rate of obesity in our community. Our finding of the influence of obesity on medication adherence was similar to a Nigerian antihypertensive adherence trial, where in addition to obesity, found a relationship between medication adherence and initial SBP which was not significant in our study.[30]

The number of medications is another determinant of medication adherence. Similar to Grezzana et al., polypharmacy or multiple pills was not associated with medication adherence. This is however contrary to other studies that found that those on multiple medications were less likely to be adherent.[25],[26] Educational level, alcohol use, and duration of hypertension were not associated with medication adherence in this current study.

Ambulatory BP measurements rather than one point clinic BP check may be more informative and helps in defining true and apparent uncontrolled hypertension.[31] In the current study, a third had true uncontrolled hypertension with no significant association with adherence. However, greater proportions of non-adherers having poor full time, daytime and nighttime systolic and DBP. Four in five participants lacked nocturnal drop in the BP which was worse in women. Non-dippers and those with nocturnal hypertension have 3–5 fold risk of developing major cardiovascular events such as stroke, heart attack and kidney failure.[32] In a study, it was shown that non-dipping and nocturnal hypertension were more frequent among hypertensives with or without kidney diseases compared with apparently normal population.[33] The presence of poor drug adherence and abnormal circadian BP variation among this population may as well explain the increasing incidence and prevalence of stroke and heart attack in the community.[34],[35]

Study strength and limitation

To the best of our knowledge, this is the first study that assessed an association between medication adherence and 24 h-ABPM among the uncontrolled hypertensive population in Nigeria. We provide evidence that ABPM is useful in determining true uncontrolled hypertension. While knowledge of hypertension was shown to be an independent predictor of adherence, this did not translate to good BP control.

One limitation of this study was the use of a self-reported questionnaire which might introduce recall bias by participants since their cognitive functions were not assessed. Furthermore, the performance of only one 24-h ABPM measurement could interfere with the reproducibility of measurements, particularly for the nocturnal BP dip. In addition, the small sample size and cross-sectional study design are a limitation to the determination of causal relationship. Larger sample size and prospective study are required to further elucidate the findings in this study.


  Conclusion Top


This study shows that high medication adherence is low in our cohort. A third had true uncontrolled hypertension while majority lacked nocturnal BP dip. Knowledge was an independent predictor of medication adherence with no significant effect on BP control. High medication adherence rather than moderate adherence, and knowledge are probably what is indeed needed for adequate BP control. This should be factored into patient education since knowledge is an independent determinant of adherence. Ambulatory BP measurement should be part of proper hypertension management.

Acknowledgement

The authors would like to appreciate Miss. Aderonmu Olajumoke and Mr. Mayowa Olatedun for their roles in the collection and entry data from the participants. Our appreciation also goes to all the participants for their cooperation in making this study a success.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
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    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]



 

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