Medicine

OBSERVATIONAL STUDY

Medication Adherence and Blood Pressure Control Among

Hypertensive Patients With Coexisting Long-Term
Conditions in Primary Care Settings
A Cross-Sectional Analysis
Yu Ting Li, MPH, Harry H.X. Wang, PhD, Kirin Q.L. Liu, MPhil, Gabrielle K.Y. Lee, MPH,
Wai Man Chan, MSc, Sian M. Griffiths, FFPH, FRCP, and Ruo Ling Chen, PhD, FRSM

Abstract: Hypertension is a typical example of long-term disease long-term conditions. Binary logistic regression analysis was conducted
posing formidable challenges to health care. One goal of antihyperten- with medication adherence and multimorbidity as outcome variables,
sive therapy is to achieve optimal blood pressure (BP) control and respectively, after controlling for effects of patient-level covariates.
reduce co-occurring chronic conditions (multimorbidity). This study The prevalence of multimorbidity was 47.4% (95% confidence
aimed to assess the influence of multimorbidity on medication adher- interval [CI] 45.4%–49.4%) among a total of 2445 hypertensive
ence, and to explore the association between poor BP control and patients. The proportion of subjects having 0, 1, and 2 additional
multimorbidity, with implications for hypertension management. long-term conditions was 52.6%, 29.1%, and 18.3%, respectively. The
A cross-sectional design with multistage sampling was adopted to overall rate of poor adherence to medication was 46.6%, whereas the
recruit Chinese hypertensive patients attending general out-patient clinics rate of suboptimal BP control was 48.7%. Albeit the influence of
from 3 geographic regions in Hong Kong. A modified systemic sampling multimorbidity on medication adherence was not found to be statisti-
methodology with 1 patient as a sampling unit was used to recruit cally significant, patients with poorly controlled BP were more likely
consecutive samples in each general out-patient clinic. Data were col- to have multimorbidity (adjusted odds ratio 2.07, 95% CI 1.70–2.53,
lected by face-to-face interviews using a standardized protocol. Poor BP P < 0.001). Diabetes was the most prevalent concomitant long-term
control was defined as having systolic BP/diastolic BP 130/80 mm Hg condition among hypertensive patients with poor BP control (38.6%,
for those with diabetes or chronic kidney disease; and 140/90 mm Hg for 95% CI 35.8–41.4 vs 19.7%, 95% CI 17.5–21.9 for patients with good
others. Medication adherence was assessed by a validated Chinese version BP control, P < 0.001).
of the Morisky Medication Adherence Scale. A simple unweighted Multimorbidity was common among hypertensive patients, and was
enumeration was adopted to measure the combinations of coexisting associated with poor BP control. Subjects with coexisting diabetes,
heart disease, or chronic kidney disorder should receive more clinical
attention to achieve better clinical outcomes.
(Medicine 95(20):e3572)
Editor: Daryle Wane.
Received: December 12, 2015; revised: April 8, 2016; accepted: April 11, Abbreviations: BP = blood pressure, MMAS = Morisky
2016. Medication Adherence Scale.
From the Community Research and Clinical Trials Unit, Zhongshan
Ophthalmic Center, Sun Yat-Sen University, Guangzhou, P.R. China
(YTL); JC School of Public Health and Primary Care, Faculty of Medicine,
The Chinese University of Hong Kong, Hong Kong (YTL, KQLL, GKYL,
WMC, SMG); School of Public Health, Sun Yat-Sen University, INTRODUCTION
Guangzhou, P.R. China (HHXW); and Centre for Health and Social Care
Improvement, University of Wolverhampton, Wolverhampton, UK (RLC).
Correspondence to: Harry H.X. Wang, School of Public Health, Sun Yat-
H ypertension is one of the most prevalent long-term diseases
seen in primary care settings in many countries. High
blood pressure (BP) is often asymptomatic; yet it accounts
Sen University, No. 74 Zhongshan Road 2, Guangzhou 510080, P.R.
China (e-mail: [email protected]). for approximately half of the incidence of stroke and ischemic
The result of this study was presented at the American Heart Association heart diseases worldwide, posing a formidable challenge to
High Blood Pressure Research 2014 Scientific Sessions, September 9-12, health care.1,2 There is a tendency for risk factor clustering
2014, San Francisco, USA: 14-HBPR-A-179-AHA-ABSTRACT410. among hypertensive patients.3,4 More importantly, the number
HHXW conceived the study. Data collection was mainly done by KQLL,
HHXW, and GKYL. YTL cleaned and analysed the data. HHXW wrote needed to treat to prevent a cardiovascular event or a death from
the first draft of the report. YTL and HHXW revised subsequent draft. All all causes is significantly lower among hypertensive patients
authors contributed to and approved the final report. with added cardiovascular diseases or other complications,
This work was supported by the Direct Grant, Faculty of Medicine, The when compared with hypertension alone.5 Multimorbidity,
Chinese University of Hong Kong. HHXW was supported by New
Faculty Start-Up Research Fund, Sun Yat-Sen University (51000- often defined as the coexistence of more than 1 long-term
18821202). The funding body has no role in the design of the study, condition within 1 subject,6 represents a critical healthcare
collection and analysis of data, and decision to publish. issue internationally.6– 9 A study with a large, nationally repre-
The authors have no conflicts of interest to disclose. sentative sample in Scotland, UK, showed that there were more
Copyright # 2016 Wolters Kluwer Health, Inc. All rights reserved.
This is an open access article distributed under the Creative Commons people living with multimorbidity than a single disease alone.10
Attribution-NonCommercial-NoDerivatives License 4.0, where it is The co-existing long-term conditions have many challenges,11
permissible to download, share and reproduce the work in any medium, including higher treatment burden7and more complex health-
provided it is properly cited. The work cannot be changed in any way or care need.10,12
used commercially.
ISSN: 0025-7974 Similar to the that in the United Kingdom, the public
DOI: 10.1097/MD.0000000000003572 healthcare sector in Hong Kong provides primary care services

Medicine  Volume 95, Number 20, May 2016 www.md-journal.com | 1

Li et al Medicine  Volume 95, Number 20, May 2016

that are heavily subsidised by the government. The majority of patient visits daily in each clinic, excluding evening clinic
chronic disease care is delivered by primary care physicians sessions. In the third stage, a modified systemic random
working at the general out-patient clinics (GOPCs).13 The load sampling methodology with 1 patient as a sampling unit was
of Chinese adult patients with hypertension is increasing.14 A used to recruit consecutive samples in each GOPC. We divided
Hong Kong Reference Framework for Hypertension Care for the estimated number of hypertensive patients visiting the
Adults in Primary Care Settings was firstly released in 2010 to practice on the day of recruitment (Ntotal) by the number of
enhance the disease management of hypertension in primary hypertensive patients planned to recruit on that day (Npro-
care.15 It consisted of a series of different modules addressing posed), which gave a number X. An integer was then randomly
various components of disease management including preven- selected from 1 to X, say 3, and the 1st, 4th, 7th, 10th, . . .,
tion, early identification, clinical care, and patient empower- consecutive patients were invited to participate in the study. The
ment. The ultimate goal of hypertension management is to total number of patients recruited in each clinic was determined
obtain maximal reduction in cardiovascular morbidity and by the population proportion in the respective region.
mortality through BP-lowering strategy. Antihypertensive
medication therapy plays an important role to achieve optimal Outcome Variables and Covariates
BP control and reduce co-occurring chronic conditions. The Optimal BP control was defined as having a clinical
benefits from patients’ adherence to antihypertensive therapies measurement of systolic BP (SBP) <140 mm Hg and diastolic
could be reflected by substantial reductions in the incidence of BP (DBP) <90 mm Hg, whereas for patients with diabetes
stroke (by 35%–40%), myocardial infarction (by 20%–25%), mellitus or chronic kidney diseases, the corresponding threshold
and heart failure (by >50%).16 was SBP <130 mm Hg and DBP <80 mm Hg.15,21–24 Medi-
However, the rates of BP control remain unsatisfactory cation adherence was assessed by the 8-item Morisky Medi-
across the globe.17,18 Only 1 or 2 out of 10 patients with cation Adherence Scale (MMAS-8), which is a commonly used,
hypertension achieved optimal BP control worldwide.19 Of validated, and self-reported adherence measure of cardiovas-
patients receiving anti-hypertensive drug therapies, many cular mediations.25 The MMAS-8 total score was calculated by
remain above recommended BP targets.20 Global statics summing the values from all 8 items, with reverse coding when
showed that developed countries had slightly higher BP necessary. A cut-off score of 6 (out of a full range of 8) was used
control rate in all hypertensive patients (10.8% vs 9.8% for to identify optimal medication adherence (MMAS-8 score
males; and 17.3% vs 16.2% for females) when compared with >6).26– 28
developing countries; yet there were no significant differ- A simple unweighted enumeration of the number of
ences.19 Insufficient optimal BP control remains a major chronic diseases29,30 was adopted to measure the combinations
challenge in the community in both developed and developing of coexisting long-term conditions. International references
countries, particularly for healthcare settings heavily bur- were made to a UK definition10 and our previous study con-
dened with chronic disease care. Nevertheless, there is a ducted in China.8 To take into account the local healthcare
paucity of data investigating the adherence in medicine taking context, long-term conditions that were mostly self-reported by
in the presence of accompanying chronic conditions, and few patients in a recent territory-wide survey in Hong Kong31 were
studies have examined how BP control is linked with also included after a panel review among a family physician, 2
additional disorders among hypertensive individuals. The public health professionals, and an epidemiologist. All con-
main objectives of our study were therefore to assess the ditions were physician-diagnosed, and were either prevalent
influence of multimorbidity on medication adherence, and to among the general patients (eg, inflammatory connective tissue
explore the association between suboptimal BP control and disorders), or concomitant comorbidities related to hyperten-
multimorbidity among hypertensive patients seen in primary sion (eg, diabetes, lipid disorders, heart disease, cerebrovascular
care settings. disease, nephritis, and chronic kidney disorder). Multimorbidity
was defined as the presence of 1 or more long-term condition in
addition to hypertension.32
METHODS
Settings and Sampling Method Sample Size Estimation
The GOPCs in Hong Kong are the primary care provider The Kish L formula33: N ¼ ([Za/2]2  P  [1  P] 
for all citizens in the public healthcare sector, operated under the [1 þ m])/(d2), with Za/2 ¼ 1.96, a ¼ 0.05, was used to explore
Hospital Authority in Hong Kong. GOPCs are organized into 7 the prevalence of coexisting long-term conditions (multimor-
hospital clusters based on 3 geographic locations—the Hong bidity) among hypertensive patients. We estimated the preva-
Kong Island, Kowloon, and the New Territories. The healthcare lence of additional chronic conditions among hypertensive
services provided in GOPCs include management of both patients attending primary care settings as P ¼ 50%. The allow-
chronic conditions and episodic illnesses, covering the entire able error was set at 0.03 and the allowable missing data were
Hong Kong population. Hypertension is one of the most long- set at 0.1. The above formula gave a minimum sample size of
term conditions seen in the GOPCs.13 A multistage sampling 1986 in total, which was also deemed adequate for logistic
design was adopted in this study. In the first stage, 1 cluster was regression analysis based on the rule of thumb, suggesting a
randomly selected in each of the 3 geographic regions (Hong minimum of 10 events per predictor variable for logistic
Kong West cluster which operates 7 GOPCs in Hong Kong models.34
Island; Kowloon Central Cluster which operates 6 GOPCs in
Kowloon; and New Territories East Cluster which operates 7 Subject and Interviewer Recruitment
GOPCs in the New Territories). In the second stage, 1 GOPC When attending GOPCs, all patients need to register at the
was randomly selected in each cluster, respectively. Each GOPC reception. After registration, patients usually queue up at the
clinic is managed by approximately 10 to 15 family physicians BP-measuring station in a separate area inside the waiting hall,
with qualified clinical training. There are around 300 to 500 before consulting the physician. All patients attending on the

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Medicine  Volume 95, Number 20, May 2016 Hypertension and Multimorbidity in Primary Care

day of study recruitment were instructed to have their BP attending physician. Each interview lasted for approximately 15
measured. We followed the inclusion criteria to invite eligible to 20 minutes.
patients to participate in the study: Chinese patients aged 18
years or above; with physician-diagnosed hypertension includ- Statistical Analysis
ing both essential and secondary hypertension; already on The characteristics of all patients were compared among
antihypertensive medication regime for at least 4 weeks before those having 0, 1, and 2 additional long-term conditions by
the study; mentally capable to communicate in Chinese; and 2-tailed chi-square test (for categorical variables) and indepen-
willing to give written informed consent to participate in the dent Student t test or analysis of variance (for continuous
study. Patients with newly diagnosed hypertension on the day of variables when appropriate). Binary logistic regression
the recruitment were excluded as their medication adherence equations with backward stepwise algorithm were modeled
afterwards was unable to measure in this cross-sectional study. with medication adherence and the presence of multimorbidity
Eligible subjects were then interviewed by trained interviewers (having 1 or more long-term conditions in addition to hyper-
in a private consultation session during their clinic visits. We tension) as outcome variables, respectively. Medication adher-
recruited interviewers from university medical students and ence and BP control were also tested in 2 separate logistic
conducted 4 training sessions (delivered by KQLL and HHXW) regression models for their association with multimorbidity. We
to standardize interview processes and minimize inter- examined the absence of multicollinearity to ensure the robust-
interviewer variances. ness of all regression models. Any P values 0.05 were
A total of 2700 consecutive adult patients taking antihy- considered statistically significant. All statistical analyses were
pertensive medication were approached and 2445 patients performed using IBM SPSS Statistics 20.0 (SPSS, Chicago, IL).
completed the study (488/554 in Hong Kong Island; 738/834
in Kowloon; 1219/1312 in New Territories). The overall
response rate was 90.6%, with no significant differences among Ethics Review
study sites (chi-square test P ¼ 0.221). The sex distribution in The study was conducted with the understanding and the
nonrespondents (female, 58.8%) was similar compared with written consent of each participant. The ethical approval of the
that in participants (female, 54.2%). The major reason for study was obtained from the Cluster Research Ethics Commit-
nonparticipation was that people were too busy to complete tee of the Hospital Authority, Hong Kong (CREC-2012.346;
the onsite survey in the clinic. KC/KE-12–0185/ER-1; UW13–016) and the Survey and Beha-
vioural Research Ethics Committee of The Chinese University
Data Collection of Hong Kong. The study protocol conforms to the ethical
guidelines of the 1975 Declaration of Helsinki.
A valid questionnaire was used for data collection, with its
face validity assessed by the same research panel. A pilot study
was conducted in 1 GOPC in October 2012 to test the reliability RESULTS
of the questionnaire. The field work started from October 2012 A total of 2445 subjects participated in the study, with an
until March 2013. The questionnaire documented patients’ average age of 65.3 years (SD 11.0). The crude prevalence of
information on demographics, socioeconomic characteristics, multimorbidity was 47.4% (1159/2445), with 95% confidence
and clinical details including long-term conditions and BPs. A interval (CI) of 45.4% to 49.4% among all study subjects.
validated Chinese version of the MMAS-8 previously developed The proportion of hypertensive patients having 0, 1, and 2
by our research team26–28 was incorporated into the question- additional long-term conditions was 52.6%, 29.1%, and 18.3%,
naire. We followed a standard procedure of collecting BP respectively. Slightly more than half (53.4%) of patients had
readings in this cross-sectional survey and BP readings on satisfactory medication adherence and 51.3% had optimal
the day of patient recruitment onsite at the clinic for all study control of both SBP and DBP simultaneously. Higher crude
participants were used. All BP were measured at least 1 hour proportion of multimorbidity was observed among study
after the subject’s last meal and at least 30 minutes after participants who were older (aged 70 years and above); female
smoking or consumption of alcohol or caffeinated beverages. sex; having lower education level; retired or part-time
Before BP measurement, participants were instructed to rest in a employed; having lower monthly household income; single
sitting position for at least 10 minutes. BP was measured by living without companion; longer duration and greater
frontline nurses using a regularly calibrated random-zero sphyg- categories of antihypertensive drug use (Table 1).
momanometer in the right arm, with an appropriately sized cuff The crude percentage of subjects having multimorbidity
in a clinically standardized manner. The first and fifth Korotkoff was not significantly different between hypertensive patients
sounds were recorded as SBP and DBP, respectively. For all with poor versus good medication adherence (48.2% [549/
study participants, BP measurements were conducted 3 times in 1139] vs 46.7% [610/1306]; P ¼ 0.735), but was significantly
a sitting posture, and the mean of 3 BP readings was calculated higher among those who had poor SBP control (53.2% [572/
to determine whether BP targets were achieved. The anthropo- 1075] vs 42.8% [587/1370]; P < 0.001) and poor DBP control
metric measurements and categorization of body mass index (59.9% [285/476] vs 44.4% [874/1969]; P < 0.001) (Table 1).
(BMI) levels followed a standard protocol used in our previous When compared with hypertensive patients having poor BP
studies.35,36 Body weight was measured by a regularly cali- control, those with satisfactory BP control had significantly
brated weight scale while on light clothing, and the height was lower percentage of having coexisting long-term conditions
measured by a standiometer without wearing shoes. (22.6%, 95% CI 20.3–24.9 for patients with poor medication
A research nurse further referred to the electronic health adherence; and 19.8%, 95% CI 17.5–22.2 for patients with
record for study subjects who self-reported the presence of good medication adherence) (Figure 1).
comorbid conditions in addition to hypertension to improve the From binary logistic regression analysis, it was found that
validity of patients’ reported additional conditions through having multimorbidity seemed to be unlikely to achieve good
cross-check. Any discrepancies were addressed by the on-site adherence in antihypertensive medicine taking, although such

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Li et al Medicine  Volume 95, Number 20, May 2016

TABLE 1. Characteristics of Hypertensive Patients by the Number of Coexisting Long-term Conditions

Multimorbidity (n ¼ 1159) (47.4%)

HT þ 0 Additional HT þ 1 Additional HTþ 2 Additional


All subjects Comorbidityy Comorbidityy Comorbiditiesy
(N ¼ 2445) (100%) (n ¼ 1286) (52.6%) (n ¼ 711) (29.1%) (n ¼ 448) (18.3%) P

Age, yrs (SD) 65.3 (11.0) 63.3 (10.7) 66.0 (10.5) 70.1 (11.2) <0.001
Age groups
<50 158 (6.5%) 108 (68.8%) 43 (27.4%) 7 (3.8%) <0.001
50–59 634 (25.9%) 396 (62.4%) 158 (25.0%) 80 (12.6%)
60–69 792 (32.4%) 431 (54.4%) 213 (26.9%) 148 (18.7%)
70 861 (35.2%) 351 (40.8%) 297 (34.5%) 213 (24.7%)
Sex
Female 1326 (54.2%) 667 (50.3%) 398 (30.0%) 261 (19.7%) 0.032
Male 1119 (45.8%) 619 (55.4%) 313 (27.9%) 187 (16.7%)
Education
No formal education 360 (14.7%) 162 (45.0%) 119 (33.1%) 79 (21.9%) 0.003
Primary school 872 (35.7%) 449 (51.5%) 265 (30.4%) 158 (18.1%)
Junior secondary 486 (19.9%) 251 (51.6%) 138 (28.4%) 97 (20.0%)
Senior secondary or above 727 (29.7%) 424 (58.3%) 189 (26.0%) 114 (15.7%)
Employment
Part-time employed 455 (18.6%) 205 (45.0%) 121 (26.6%) 129 (28.4%) <0.001
Full-time employed 668 (27.3%) 389 (58.3%) 162 (24.3%) 117 (17.4%)
Retired 1322 (54.1%) 692 (52.3%) 428 (32.4%) 202 (15.3%)
Living status
Without companion 552 (22.5%) 267 (48.5%) 173 (31.4%) 112 (20.1%) 0.037
With companion 1893 (77.5%) 1019 (53.8%) 538 (28.4%) 336 (17.8%)
Monthly household income (HK$)
10,000 1262 (51.6%) 620 (49.1%) 385 (30.5%) 257 (20.4%) <0.001
10,001–20,000 562 (23.0%) 312 (55.5%) 145 (25.8%) 105 (18.7%)
20,001–30,000 292 (11.9%) 148 (50.7%) 99 (33.9%) 45 (15.4%)
>30,000 329 (13.5%) 206 (62.6%) 82 (24.9%) 41 (12.5%)
BMI (SD) 25.0 (4.2) 25.1 (4.3) 25.0 (4.0) 25.0 (4.1) 0.806
BMI categories
<18.5 kg/m2 68 (2.8%) 33 (48.5%) 17 (25.0%) 18 (26.5%) 0.312
18.5–22.9 kg/m2 748 (30.6%) 396 (52.9%) 207 (27.7%) 145 (19.4%)
23.0–27.4 kg/m2 1133 (46.3%) 587 (51.8%) 352 (31.1%) 194 (17.1%)
27.5 kg/m2 496 (20.3%) 270 (54.4%) 135 (27.2%) 91 (18.4%)
Family history of HT
No 1019 (41.7%) 538 (52.8%) 311 (30.5%) 170 (16.7%) 0.325
Yes 1426 (58.3%) 748 (52.5%) 400 (28.0%) 278 (19.5%)
Duration of taking anti-HT medications, yrs (categories)
<2 466 (19.1%) 275 (59.0%) 93 (20.0%) 98 (21.0%) <0.001
3–5 509 (20.8%) 258 (50.7%) 132 (25.9%) 119 (23.4%)
6–10 680 (27.8%) 354 (52.0%) 203 (29.9%) 123 (18.1%)
11–15 384 (15.7%) 202 (52.6%) 125 (32.6%) 57 (14.8%)
>15 406 (16.6%) 197 (48.5%) 158 (38.9%) 51 (12.6%)
N, anti-HT medications
1 1461 (59.8%) 781 (53.5%) 409 (28.0%) 271 (18.5%) 0.003
2 737 (30.1%) 401 (54.5%) 204 (27.6%) 132 (17.9%)
>2 247 (10.1%) 104 (42.1%) 98 (39.7%) 45 (18.2%)
Medication adherence
Poor adherence 1139 (46.6%) 590 (51.8%) 339 (29.8%) 210 (18.4%) 0.735
Good adherence 1306 (53.4%) 696 (53.3%) 372 (28.5%) 238 (18.2%)
SBP control
Poor 1075 (44.0%) 503 (46.8%) 362 (33.7%) 210 (19.5%) <0.001
Optimal 1370 (56.0%) 783 (57.2%) 349 (25.5%) 238 (17.3%)
DBP control
Poor 476 (19.5%) 191 (40.1%) 159 (33.4%) 126 (26.5%) <0.001

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Medicine  Volume 95, Number 20, May 2016 Hypertension and Multimorbidity in Primary Care

Multimorbidity (n ¼ 1159) (47.4%)

HT þ 0 Additional HT þ 1 Additional HTþ 2 Additional


All subjects Comorbidityy Comorbidityy Comorbiditiesy
(N ¼ 2445) (100%) (n ¼ 1286) (52.6%) (n ¼ 711) (29.1%) (n ¼ 448) (18.3%) P

Optimal 1969 (80.5%) 1095 (55.6%) 552 (28.0%) 322 (16.4%)

The monthly household income level was categorized according to the median monthly household income in Hong Kong (HK$22,400), from the
Population and Household Statistics 2013 (Census and Statistics Department, Hong Kong SAR). The BMI levels were categorized according to the
World Health Organization (WHO)-recommended cut-off points for Asian populations (2004). Poor medication adherence was defined as having
MMAS-8 score 6. Poor BP control was defined as having SBP 140 mm Hg/DBP 90 mm Hg (or SBP 130 mm Hg/DBP 80 mm Hg for patients
with concomitant diabetes or chronic kidney disease). Differences between categories among subjects with no additional morbidities, 1 additional
morbidity only, and 2 additional morbidities and above were explored by chi-square test (for categorical variables) and analysis of variance (for
continuous variables).
BMI ¼ body mass index, DBP ¼ diastolic blood pressure, HT ¼ hypertension, SBP ¼ systolic blood pressure, MMAS-8 ¼ Morisky Medication
Adherence Scale, 8 items.

Proportion across column.
y
Proportion across row.

influence was not found to be statistically significant (adjusted 95% CI 7.5–10.7) when compared with patients whose BP
odds ratio [aOR] 0.97, 95% CI 0.80–1.19, P ¼ 0.802) (Table 2). levels were below the levels considered optimal. Diabetes
On the other hand, we found that the presence of accompanying mellitus was the most prevalent concomitant long-term con-
long-term conditions was significantly associated with poor BP dition among hypertensive patients with poor BP control
control (aOR 2.07, 95% CI 1.70–2.53, P < 0.001), whereas no (Figure 2).
significant association was detected between poor medication
adherence level and multimorbidity (aOR 1.07, 95% CI 0.88– DISCUSSION
1.30, P ¼ 0.481). Older age (70 years), lower monthly house-
hold income level, longer duration of antihypertensive drug use, Statement of Principal Findings
and higher number of drug use were common contributing From this cross-sectional study of more than 2440 Chinese
factors that were significantly associated with the presence hypertensive patients, it was found that nearly half of the adult
of multimorbidity in both models, with medication adherence hypertensive subjects had coexisting long-term conditions. The
and BP control as covariates, respectively (Table 3). presence of multimorbidity was independently associated with
Hypertensive subjects with poor BP control had higher advanced age, lower household income, longer duration of
prevalence of additional long-term conditions, particularly with antihypertensive medication use, higher number of drugs taken,
regard to diabetes mellitus (38.6%, 95% CI 35.8–41.4 vs and poor BP control. We did not observe significant influence of
19.7%, 95% CI 17.5–21.9), heart disease (19.2%, 95% CI multimorbidity on patients’ adherence to antihypertensive
17.0–21.4 vs 11.9%, 95% CI 10.0–13.7), and nephritis and medications; whereas individuals with BP above the levels
chronic kidney disorder (14.5%, 95% CI 12.5–16.5 vs 9.1%, considered optimal were significantly more likely to suffer

% Subjects with multimorbidity

35%

30%

25%

20%

15%

10%

5%

0%
Poor BP control Poor BP control Optimal BP control Optimal BP control
+ Poor adherence + Good adherence + Poor adherence + Good adherence

FIGURE 1. Proportion of subjects having multimorbidity by medical adherence and blood pressure (BP) control.

Copyright # 2016 Wolters Kluwer Health, Inc. All rights reserved. www.md-journal.com | 5
Li et al Medicine  Volume 95, Number 20, May 2016

TABLE 2. Influence of Multimorbidity on Medication Adherence by Logistic Regression Analysis


Unadjusted Model Adjusted Model

OR (95% CI) P aOR (95% CI) P

Age, per 10 yrs 1.18 (1.08–1.28) <0.001 1.41 (1.02–1.96) 0.038

Sex
Female 1.00 (Ref) 1.00 (Ref)
Male 1.09 (0.93–1.28) 0.280 1.22 (1.01–1.47) 0.036
Employment
Currently employed 1.00 (Ref) 1.00 (Ref)
Retired 1.39 (1.16–1.66) <0.001 1.28 (1.02–1.61) 0.037
BP control
Poor 1.00 (Ref) 1.00 (Ref)
Optimal 1.16 (0.99–1.36) 0.072 1.19 (1.00–1.42) 0.047
Multimorbidity
No 1.00 (Ref) 1.00 (Ref)
Yes 0.88 (0.75–1.03) 0.120 0.97 (0.80–1.19) 0.802

Dependent variable: Medication adherence level (1 ¼ good; 0 ¼ poor [Morisky Medication Adherence Scale, 8 items score 6]). Independent
variables tested included age, sex, education, employment, marriage, living status, district of living, household income, body mass index, family
history, duration and number of antihypertensive drug use, BP control, and multimorbidity. Poor BP control was defined as having SBP 140 mm Hg/
DBP 90 mm Hg (or SBP 130 mm Hg/DBP 80 mm Hg for patients with concomitant diabetes or chronic kidney disease). Multimorbidity was
defined as the presence of one or more long-term condition in addition to hypertension.
aOR ¼ adjusted odds ratio, CI ¼ confidence interval, OR ¼ odds ratio, Ref ¼ reference.

Only variables that were statistically significant (P values <0.05) in the regression equation using backward stepwise algorithm were included as
covariates in the final regression model to test the association between multimorbidity and medication adherence.

from coexisting long-term conditions such as diabetes, heart outcome.40 The Danish General Practice Database study pre-
disease, or chronic kidney disorder. viously evaluated the association between multimorbidity and
rate of BP control in a large cohort of hypertensive patients
which showed that the BP control rates differed substantially
Relationship With Literature and Explanation of between patients with comorbidities.32 In particular, only
Findings 16.5% of hypertensive patients with diabetes in Danish general
Patients with multiple long-term conditions are very fre- practice had BP below 130/80 mm Hg, which was a recom-
quently encountered in routine clinical practice particularly mended therapeutic target for individuals with diabetes melli-
among those with hypertension. Previous investigations on the tus.15,21 –24 In our study where the same BP cut-off value was
determinants of medication adherence and BP control in the same used, the findings that the prevalence of diabetes was the highest
Hong Kong primary care population suggested the necessity for among individuals with poor BP control were complementary to
further research from a multimorbidity perspective.37 National earlier observations in Denmark. Another study conducted by
data collected in Scotland, UK, showed that 78% of hypertensive the British Hypertension Society pointed out that the BP of
patients seen in general practice had at least 1 other long-term <130/80 mm Hg as a rigorous target in patients with diabetes
conditions from a list of 40 chronic conditions.10 There have also may be more difficult to reach than BP targets of <140/90 mm
been heterogeneous methods used across observational studies to Hg.41 Further research might need to identify the ideal BP level
define multimorbidity among different study populations. An at which maximum protection against diabetic complications is
earlier systematic review38 showed that the proportion of multi- conferred, and below which the reduction no longer delivers a
morbidity increased as age advanced, and its prevalence in older benefit that exceeds risk42 for the diabetes population of differ-
persons ranged from 55% to 98%, suggesting considerable dis- ent age groups, particularly for the Asian population. Another
ease complexity and enormous burden on health care. In our explanation could be that some physicians may consider 140/
study, the crude proportion of multimorbidity was lower than that 90 mm Hg as ‘‘close enough to target,’’ and with clinical inertia,
reported in the United Kingdom, which may be due (at least in physicians prefer to only deal with the most pressing or
part) to the differences in the number of chronic diseases con- symptomatic problem alone while observing if the BP level
sidered and the data collection approach used. We found that the is not very high. It is also possible that the perceptions of
household income level was an independent factor associated physicians towards optimal BP control may be different
with multimorbidity, meaning that hypertensive subjects living in between patients with or without multimorbidities.43 In contrast
deprived household were more likely to confront multiple comor- to the methodology used in a more recent UK study in which
bid conditions. The findings are compatible with previous studies multiple SBP measures collected from the Lambeth DataNet
in the western countries, reporting that with higher degrees were analyzed as continuous variables,44 it is worth noting that
of deprivation, the mix of multiple medical problems our study sought to identify success or failure in achieving the
become greater,9,10 or what has been recognized as the ‘‘inverse BP target. The perspective on BP control provides real-world
care law.’’39 clinical insights as lowering BP to particular target values often
There is a large volume of epidemiological evidence that represents a more difficult issue. Although there is a need to
consistent BP control is linked with improved cardiovascular exercise some caution in the interpretation as we were unable to

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Medicine  Volume 95, Number 20, May 2016 Hypertension and Multimorbidity in Primary Care

TABLE 3. Factors Association With the Presence of Multimorbidity Among Hypertensive Patients

Unadjusted Model Adjusted Model 1 Adjusted Model 2y

OR (95% CI) P aOR (95% CI) P aOR (95% CI) P

Age, yrs
<50 1.00 (Ref) 1.00 (Ref) 1.00 (Ref)
50–59 1.32 (0.91–1.91) 0.146 1.06 (0.68–1.65) 0.809 1.10 (0.70–1.71) 0.688
60–69 1.82 (1.27–2.62) 0.001 1.41 (0.91–2.19) 0.125 1.48 (0.95–2.31) 0.082
70 3.17 (2.20–4.55) <0.001 2.39 (1.52–3.76) <0.001 2.37 (1.50–3.74) <0.001
Monthly household income (HK$)
>30,000 1.00 (Ref) 1.00 (Ref) 1.00 (Ref)
20,001–30,000 1.65 (1.19–2.27) 0.002 1.06 (0.77–1.46) 0.708 1.11 (0.81–1.53) 0.521
10,001–20,000 1.36 (1.03–1.79) 0.031 1.05 (0.75–1.47) 0.773 1.11 (0.79–1.57) 0.544
10,000 1.76 (1.37–2.26) <0.001 1.52 (1.04–2.22) 0.030 1.54 (1.05–2.26) 0.027
Use of antihypertensive drugs
Duration, per yr 1.01 (1.00–1.02) 0.053 1.02 (1.01–1.04) <0.001 1.02 (1.01–1.04) 0.001
N, anti-HT medications
1 1.00 (Ref) 1.00 (Ref) 1.00 (Ref)
2 0.96 (0.80–1.15) 0.648 0.87 (0.70–1.09) 0.227 0.85 (0.68–1.06) 0.160
>2 1.57 (1.20–2.06) 0.001 1.52 (1.10–2.10) 0.012 1.58 (1.14–2.20) 0.006
Medication adherence
Good (MMAS >6) 1.00 (Ref) 1.00 (Ref) –
Poor (MMAS 6) 1.06 (0.91–1.25) 0.449 1.07 (0.88–1.30) 0.481 – –
BP control
Optimal BP control 1.00 (Ref) – 1.00 (Ref)
Poor BP control 1.60 (1.37–1.88) <0.001 – – 2.07 (1.70–2.53) <0.001

Dependent variable: presence of multimorbidity (1 ¼ yes; 0 ¼ no). Independent variables tested included age, sex, education, employment,
marriage, living status, district, household income, body mass index, family history, medication adherence, duration and number of antihypertensive
drug use, and BP control.
aOR ¼ adjusted odds ratio, CI ¼ confidence interval, MMAS ¼ Morisky Medication Adherence Scale (8 items), OR ¼ odds ratio, Ref ¼ reference.

Only variables that were statistically significant (P values <0.05) in the regression equation using backward stepwise algorithm were included as
covariates in the final regression model to test the association between medication adherence and multimorbidity.
y
Only variables that were statistically significant (P values < 0.05) in the regression equation using backward stepwise algorithm were included as
covariates in the final regression model to test the association between blood pressure control and multimorbidity.

% Subjects with coexisting long-term conditions

45%
Optimal BP control
40%
Poor BP control
35%

30%

25%

20%

15%

10%

5%

0%
Diabetes Lipid disorders Heart disease Cerebrovascular Chronic kidney Connective
mellitus disease disorder tissue disorders

FIGURE 2. Prevalence of major coexisting long-term conditions among participants by blood pressure (BP) control.

Copyright # 2016 Wolters Kluwer Health, Inc. All rights reserved. www.md-journal.com | 7
Li et al Medicine  Volume 95, Number 20, May 2016

comprehensively retrieve from the entire subjects a whole measurement alone instead of an average over a period of time.
spectrum covering all previous BP measurements in past visits, One may argue that people with ’masked hypertension’ would
the evidence from our findings suggests that the focus on be misclassified, albeit this phenomenon was seen much more
achieving good BP control in the Chinese population should frequently in younger patients. Given that those under 50 years
not be neglected. of age only accounted for a very small proportion (6.5%), the
Previous literature has suggested that patient nonadherence effects of possible misclassification of ’masked hypertension’
to prescribed antihypertensive therapy could serve as a major on the study results were therefore considered minimum.
obstacle to achieving good clinical outcomes.45 In our study,
however, we did not detect a significant association between Conclusions and Future Prospects
medication adherence and the presence of multimorbidity. It This study indicated that hypertensive patients presented
might be that having accompanying chronic conditions requires with poor BP control should be evaluated in a more meticulous
higher intensity and complexity of treatment regime such that manner for the possible presence of other coexisting medical
polypharmacy and multiple daily dosing may reduce the drug conditions, in particular, diabetes. On the other hand, hyper-
adherence.45,46 One may argue otherwise that the presence of tensive patients with multimorbidity should have their BP
multimorbidity may be linked with increased adherence to the monitored more closely as they tended to have poorer BP
medication because of the perceived seriousness of multiple control. This has important implications for both policy makers
conditions47; despite that, we did not collect such information. and physicians, because the high prevalence of multimorbidity
Nevertheless, it seems likely that hypertensive subjects were points towards the need to prioritize more healthcare resources
prone to have poor adherence to medications in the presence of to address the multiple medical conditions among hypertensive
concomitant long-term conditions based on our study findings, patients. It was well-recognised that earlier detection of shared
albeit such association was not statistically significant. We risk factors could lead to better clinical outcomes by reducing
therefore speculated that the association might be mediated long-term complications.53 From a healthcare system’s point of
by factors such as prescription pattern, treatment intensification, view, health services delivery should be reviewed and oriented
or health behaviors,48 which needs further in-depth causal to address the rising challenges of multimorbidity.54,55 These
investigation. The US National Health and Nutrition Examin- include combined efforts to enhance continuity of care, coordi-
ation Study depicted a picture of unsatisfactory BP control, nation among different healthcare professionals, and the pro-
despite the awareness of hypertension among people who were mulgation of adopting holistic care models. The findings also
more likely to be taking antihypertensive medications.49 Our call for more prospective studies to evaluate the effect of
results that coexisting diabetes, heart disease, or chronic kidney multidrug prescribing patterns on multimorbidity, and the best
disorder was more prevalent in people with poor BP control also primary care-based interventional strategies to handle the com-
echoed earlier US studies in which adults with diabetes had the plexity of hypertension management which demands urgent
greatest population burden of uncontrolled BP, followed by attention.
adults with chronic kidney disease and cardiovascular disease.49
A study in Australia showed that multimorbidity could lead to
difficulties in pharmaceutical care management in primary ACKNOWLEDGMENTS
care.50 Given that most medication treatments are delivered We thank healthcare staff from Central Kowloon Health
according to single-disease-oriented guidelines,51 the explora- Centre (Kowloon), Wong Siu Ching Family Medicine Centre
tion of appropriateness of medication prescriptions among (New Territories), and Tsan Yuk Hospital-General Outpatient
multimorbid hypertensive patients is warranted. Clinics (Hong Kong Island), whose support ensured high-
quality data collection.
Strengths and Limitations of the Study
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