LDL-C TARGET ACHIEVEMENT, FACTORS

ASSOCIATED WITH NONACHIEVEMENT

OF LDL-C TARGET AND ADHERENCE TO
STATIN THERAPY AMONG PATIENTS WITH
TYPE 2 DIABETES MELLITUS

A thesis submitted for the Degree of Master of Family Medicine

CANDIDATE NO: T3006

NOVEMBER 2014

Table of Contents
LIST OF TABLES......................................................................................................................v
LIST OF FIGURES..................................................................................................................vi
ABBREVIATIONS..................................................................................................................vii
ABSTRACT..............................................................................................................................ix
English Version.....................................................................................................................ix
Malay Version.......................................................................................................................xi
CHAPTER 1...............................................................................................................................1
INTRODUCTION..................................................................................................................1
1.1 Dyslipidaemia and Cardiovascular disease.....................................................................1
1.2 Dyslipidaemia and Diabetis Mellitus...............................................................................2
1.3 Low Density Lipoprotein Cholesterol..............................................................................3
Justification of research..........................................................................................................5
CHAPTER 2...............................................................................................................................6
LITERATURE REVIEW.......................................................................................................6
2.1 LDL-C target in Dyslipidaemia and Type 2 Diabetes Mellitus....................................6
2.2 Statin therapy in dyslipidaemia....................................................................................7
2.2 LDL-C Achievement and its associated factors...........................................................9
2.3 Medication adherence.................................................................................................11
2.4 LDL achievement and adherence...............................................................................14
CHAPTER 3.............................................................................................................................15
OBJECTIVES......................................................................................................................15
3.1 General Objectives.........................................................................................................15
3.2 Specific objectives.........................................................................................................15
3.3

RESEARCH HYPOTHESIS.....................................................................................15

3.4

Operational definition................................................................................................16
2

CHAPTER 4.............................................................................................................................17
METHODOLOGY...............................................................................................................17
4.1 Study design...................................................................................................................17
4.2 Study area.......................................................................................................................17
4.3 Population and sample...................................................................................................17
4.3.1 Reference population..............................................................................................17
4.3.2 Source population....................................................................................................18
4.3.3 Study population.........................................................................................................18
4.3.4 Inclusion criteria.....................................................................................................18
4.3.5 Exclusion Criteria...................................................................................................18
4.3.6 Sampling method...................................................................................................19
4.3.7 Sample size calculation..............................................................................................19
4.4 Research tools................................................................................................................23
4.5 Statistical analysis..........................................................................................................25
4.5.1

The procedure of multiple logistic regression....................................................26

4.6 Ethical consideration......................................................................................................27

CHAPTER 5.............................................................................................................................30
RESULT...............................................................................................................................30
5.1

Socio-demographic characteristic of respondents.....................................................30

5.2 Clinical characteristics of respondants...........................................................................31

5.3 Proportion of LDL-C goal achievers and nonachievers.................................................34
5.4 Proportion of adherence to statin therapy......................................................................35
5.5 The associated factors to nonachievement of LDL-C target among patients with Type 2
Diabetes Mellitus.................................................................................................................36
5.5.1 The associated factors to nonachievement of LDL-C target by Simple Logistic
regression.........................................................................................................................36
5.5.2 The Associated factors to nonachievement of LDL-C target by Multiple Logistic
Regression........................................................................................................................39
3

CHAPTER 6.............................................................................................................................41
DISCUSSION......................................................................................................................41
6.1 Proportion of LDL-C goal achievers and nonachievers among patients with Type 2
Diabetes Mellitus.................................................................................................................41
6.2

Percentage of adherence to statin therapy and relationship with..............................43

LDL-C target achievement...................................................................................................43

6.3

The associated factors to nonachievement of LDL-C target.....................................46

6.3.1

Sociodemographic factors..................................................................................46

6.3.2

Clinical factors...................................................................................................47

CHAPTER 7.............................................................................................................................51
CONCLUSIONS..................................................................................................................51
CHAPTER 8.............................................................................................................................52
LIMITATIONS OF THE STUDY........................................................................................52
RECOMMENDATIONS......................................................................................................54
REFERENCES.........................................................................................................................55

LIST OF TABLES
Table 4.1: Sample size culculation for categorical variables...................................................22
Table 4.2: Sample size culculation for numerical variables.....................................................22
Table 5.1: Socio-demographic characteristic of respondents...................................................30
Table 5.2: Clinical characteristics of respondants....................................................................32
Table 5.3: Association between sociodemographic factors and nonachievers of LDL-C target
screening by Simple Logistic Regression................................................................................36
Table 5.4: Association between clinical data and nonachievers of LDL-C target screening by
Simple Logistic Regression......................................................................................................37
Table 5.5: Associated factors to nonachievement of LDL-C target by Multiple Logistic
Regression................................................................................................................................39

LIST OF FIGURES
Figure 4.1 Flow chart of the study...........................................................................................28
Figure 4.2 Conceptual framework of study..............................................................................29
Figure5.1The proportion of LDL cholesterol achievement among patients with Type 2
Diabetes Mellitus......................................................................................................................34
Figure 5.2The percentage of patients with Type 2 Diabetes Mellitus in adherence to statin
therapy......................................................................................................................................35

LIST OF APPENDIXES
Appendix I

Ethic approval from university Research Ethics Committee

62

Appendix II

Approval from Hospital

63

Appendix III

Consent form

64

Appendix IV

Case Report Form

69

Appendix V

Questionnaire

72

ABBREVIATIONS

ACS

Acute Coronory Syndrome

CHD

Coronory Heart Disease

DBP

Diastolic Blood Pressure

DM

Diabetes Mellitus

HDL

High Density Lipoprotein

HUSM

Hospital Universiti Sains Malaysia

KRK

Klinik Rawatan Keluarga

LDL-C

Low Density Lipoprotein Cholesterol

MCQ

Medication Compliance Questionnaire

NCEP-ATP

National Cholesterol Education Program Adult Treatment Panel

SBP

Systolic Blood Pressure

TG

Triglyceride

WHO

World Health Organisation

ABSTRACT
English Version

Tittle: Low Density Lipoprotein Cholesterol target achievement, factors associated with
nonachievers and adherence to statin therapy among patients with Type 2 Diabetes Mellitus.

Introduction: Globally, cardiovascular disease is the leading cause of mortality and morbidity.
Dyslipidaemia is a risk factor for cardiovascular disease and Type 2 Diabetes Mellitus is a
cardiovascular risk equivalent. Low density lipoprotein cholesterol (LDL-C) is the primary
target in the management of dyslipidaemia and achievement of LDL-C target according to
National Cholesterol Education Programme (NCEP-ATP III) is crucial.
Statins are potents drug to reduce cholesterol especially the LDL-C,

however the

effectiveness is limited by the poor adherence.

Objectives: To determine proportion of LDL-C target achievement, factors associated with

nonachievers and the adherence to statin therapy among patients with Type 2 Diabetes
Mellitus.

Methodology: A cross sectional study involving 234 patients aged 18 years old and above
who had comorbid Type 2 Diabetes Mellitus and Dyslipidaemia. Systematic Random
Sampling with replacement method was applied to select participants who attended KRK,
HUSM from January 2013 to May 2013. Both self-administered and interviewered
administered questionnaires were

used to obtain the socio demographic characteristics,

clinical characteristics and compliance questionnaire. The data was analysed for descriptive
statistic and multiple logistic regression.
Result: The percentage of LDL-C target achievement was 37.6%. The percentage of patients
adhered to statin therapy was 98.3% and 20.5% of patients adhered fully. There was no
significant relation between LDL-C achievement and adherence. Sociodemographic
data(such as age, marital status, gender, education level and household income) and clinical
data (such as smoking status, number of prescribed medications, BMI, SBP, duration on
statin therpy and type of statin taken.) were not associated with achievement of LDL-C target.
HbA1c is the only significant factor that associated with LDL-C target achievement.

Conclusion: Achievement of low density lipoprotein target among Type 2 Diabetes Mellitus

patients attended KRK,HUSM was still low. Majority patients were adhered to statin therapy
however the relation between adherence and LDL-C achievement was not significant. HbA1c
was the only significant factor associated to LDL-C.

10

Malay Version

Tajuk: Pencapaian sasaran kolesterol lipoprotein ketumpatan rendah dan faktor-faktor yang
mempengaruhi bukan pencapai dan kepatuhan terhadap ubat kolesterol jenis statin

di

kalangan pesakit Kencing Manis Jenis 2.

Pengenalan: Di peringkat global, penyakit kardiovaskular merupakan punca utama

kematian dan morbiditi. Dyslipidaemia adalah faktor risiko bagi penyakit kardiovaskular dan
penyakit Kencing Manis jenis 2 adalah risiko kardiovaskular yang setara. Kolesterol
lipoprotein ketumpatan rendah adalah sasaran utama dalam pengurusan dyslipidaemia dan
pencapaiannya mengikut National Cholesterol Education Programme (NCEP-ATP III) adalah
penting. Statin adalah ubat antikolesterol yang berkesan untuk mengurangkan kolesterol
terutamanya

kolesterol

lipoprotein

ketumpatan

rendah.

Walau

bagaimanapun

keberkesanannya adalah terhad disebabkan oleh ketidakpatuhan terhadap ubat antikolesterol.

Objektif: Untuk menentukan tahap pencapaian sasaran koleterol lipoprotein ketumpatan

rendah, faktor-faktor yang mempengaruhi bukan pencapai dan peratus kadar pematuhan
terhadap ubat kolesterol jenis statin.

Metodologi: Ini adalah kajian rentas yang melibatkan seramai 324 pesakit berumur 18 tahun
dan ke atas yang menghidapi penyakit Kencing Manis Jenis 2. Pemilihan sampel secara
Sistematik Rambang telah dilakukan untuk memilih peserta yang datang ke KRK, HUSM
dari Januari 2013 hingga Mei 2013. Borang soal selidik telah digunakan untuk mendapatkan

11

ciri-ciri sosio demografi, ciri-ciri klinikal dan soal selidik pematuhan terhadap ubat. Data
yang diperolehi telah dianalisis menggunakan statistik deskriptif dan regresi logistik
berganda.

Keputusan: Peratusan pencapaian sasaran kolesterol lipoprotein ketumpatan rendah adalah

37.6%. Peratus pematuhan kepada ubat kolesterol jenis statin adalah 98.3% dan 20.5%
pesakit telah patuh sepenuhnya. Tiada hubungan yang signifikan antara tahap pencapaian
kolesterol lipoprotein ketumpatan rendah dan pematuhan terhadap ubat kolesterol jenis statin.
Data sosiodemografi (seperti umur, status perkahwinan, jantina, tahap pendidikan dan
pendapatan isi rumah) dan data klinikal (seperti status merokok, jumlah ubat-ubatan diambil,
jisim index badan, tekanan darah sistolik, tempoh menggunakan ubat kolesterol jenis statin
dan jenis statin yang diambil) tidak mempunyai kaitan dengan tahap pencapaian sasaran
kolesterol lipoprotein ketumpatan rendah. HbA1c merupakan satu-satunya faktor yang
ditemui mempunyai kaitan dengan tahap pencapaian lipoprotein ketumpatan rendah.

Kesimpulan: Pencapaian sasaran kolesterol lipoprotein ketumpatan rendah di kalangan

pesakit Kencing Manis Jenis 2 di KRK, HUSM adalah masih rendah. Majoriti pesakit telah
patuh terhadap pengambilan ubat kolesterol jenis statin. HbA1c adalah satu-satunya faktor
signifikasi yang mempunyai perkaitan dengan tahap pencapaian kolesterol lipoprotein
ketumpatan rendah.

12

CHAPTER 1

INTRODUCTION

1.1 Dyslipidaemia and Cardiovascular disease

Cardiovascular disease include coronory heart disease, cerebrovascular disease and

peripheral arterial disease. Coronory heart disease is a spectrum of stable angina, ischaemic
heart disease and myocardial infarction. According to Ministry of Health Malaysia,
cardiovascular disease was the leading cause of death in 2009 for both men and women. In
2008, World Health Organization reported that cardiovascular disease is the top leading cause
of death in the world among countries with average and high incomes which accounted about
13% to 16% of death. National Cardiovascular Disease Acute Coronory Syndrome Registry
(NCVD-ACS 2006-2008) reported that there is a high prevalence of established
cardiovascular risk factor among patients with ACS which is rated at 31% to 35% in which
patients had history of dyslipidaemia and in overall, 55.9% had abnormal cholesterol level(1).

Dyslipidaemia is a major risk factor for cardiovascular disease(2). Many

epidemiologic studies have shown that dyslipidaemia is a strong predictor of the likelihood
that an individual will developed cardiovascular disease. High LDL and low HDL has been
demonstrated as risk factors which are causally linked to cardiovascular disease(2).

The Strong Heart Study assessed the cardiovascular disease risk factors in diabetic
individuals. In this large cohort study, it was found that LDL cholesterol was a strong
independent predictor of coronory heart disease and hazard ratio indicates that a
10mg/dL(0.6mmol/l) increase in LDL choleserol levels would lead to a 12% increase in
cardiovascular disease(3). It is crucial to manage dyslipidaemia accordingly and
pharmacological treatment should be initiated early if indicated. To achieve the target of
controlled blood cholesterol level is not only done through

drug therapy but also

simultanously with the therapeutic changes of life style. A 12 years follow up study in the
Russian Lipid Research Clinics observed a contradictory finding regarding association of risk
of coronory heart disease and cholesterol level(4). Men with very low LDL-C had increased
in coronory heart disease mortality and was described as a J-shaped curve. CHD death rate in
men Russian patients with LDL-C less than 2.9mmol/l was slightly higher than patients with
LDL-C between 2.9mmol/l to 3.4mmol/l resulting a J-shaped curve. However, they concluded
that the J-shaped relationship between LDL and CHD mortality was associated with lifestyle
characteristic such as low educational achievement, high alcohol consumption, higher history
of current smoking and lower mean BMI.

1.2 Dyslipidaemia and Diabetis Mellitus

Type 2 Diabetes Mellitus had more significant impact to the development of multiple
microvascular and macrovascular complications including coronary heart disease. Major
clinical trials such as Multiple Risk Factor Intervention (MRFIT), The Prospective
Cardiovascular Munster Study (PROCAM) and The Framingham Heart Study had shown
relationship between Diabetes Mellitus and Coronory Heart Disease mortality(5-7). National
Health Morbidity Survey in 2011 found that 35.1% of adult aged 18 years old and above had
2

hypercholesterolaemia and suprisingly 26.6%

were previously undiagnosed with

hypercholesterolaemia(8).

Dyslipidaemia and Diabetes Mellitus are major predictors for cardiovascular disease
as both clinical condition have an effect towards macrovascular disease and formation of
artherogenesis (9). Individual with both clinical conditions are considered to be at a higher
risk in developing cardiovascular disease and treating to target is really important to prevent
further morbidity and mortality resulting from cardiovascular events.

The more recently recognised features are small dense LDL-C and excessive
postprandial lipemia(10). Small dense LDL-C particles easily penetrate the vascular
endothelium and get deposited in the walls of the vessels(11). The percentage of individuals
possessing small and dense LDL-C is higher by at least 2 folds in T2DM(11). Among patients
with established cardiovascular disease or cardiovascular risk equavalent, pharmacotherapy
should begin with adjuvant to therapeutic lifestlye modification including exercise and dietery
intervention. LDL C is the primary target for therapy and is dependant upon an individuals
global cardiovascular risk.

1.3 Low Density Lipoprotein Cholesterol

Low density lipoprotein (LDL) is one of the five major groups of lipoproteins and the
cholesterol which is bind to it is known as LDL cholesterol or is also well known as a bad
cholesterol. The five major lipoproteins including chylomicrons, very low density lipoprotein
(VLDL), intermediate density lipoprotein (IDL), low density lipoprotein and high density
3

lipoprotein varies in the term of size from largest to smallest. These lipoproteins have a
function for transporting lipids like cholesterol and tryglycerides within the water based
blood stream. LDL particles are very similar in size to the normal gaps in the endithelium.
LDL particles can transport cholesterol into the arterial wall and be retained as arterial
proteoglycans which attract macrophages that engulf the LDL particles and start the formation
of plaques. These condition increased the risk of atherosclerosis. The atherogenicity of LDL
cholesterol is well established and proven in many studies. Most of the major clinical trials
have shown a direct relationship between level of LDL cholesterol and the risk of coronory
heart disease either in a previously healthy population or in patients with the related diseases
such as hypertension and diabetes mellitus. National Cholesterol Education Programme
Adult Treatment Plan I to III (NCEP-ATP III) has established LDL cholesterol as a primary
target of therapeutic interaction because LDL cholesterol plays a major role in initiating the
development of atherosclerotic plaque. Meta analysis have shown that reducing total
cholesterol by 1mmol/l significantly reduces mortality due to coronory heart disease(12).

Justification of research

This research is conducted to determine primary lipid target achievement which is low
density lipoprotein cholesterol and the adherence to statin therapy in patients with comorbid
Type 2 Diabetes Mellitus and Dyslipidaemia. National Cholesterol Education Programme
Adult Treatment Plan I to III (NCEP-ATP I -III) has established LDL cholesterol as a primary
target of therapeutic interaction because LDL cholesterol plays a major role in initiating the
development of atherosclerotic plaque. It is crucial to achieve the target of LDL-C according
to the recommended level as it prevent further risk of cardiovascular event. This study
evaluated the current performance of LDL-C achievement in patients with Type 2 Diabetes
Mellitus and reflected the management of dyslipidaemia of Type 2 Diabetes Mellitus. The
adherence to lipid lowering therapy particularly statin group which was stated as the most
potent antilipid in reducing LDL-C level is also important. Being aware of the factors
associated with LDL-C achievement, can assist us in recognising patients which have
tendency to become non-achievers to LDL-C target. It is also important to identify underlying
socioeconomic and lifestyle-related factors in order to begin

appropriate interventions and

management.

Our primary health care setting has a vast array of patients charactheristic with
demographic differences, patients from the rural areas, semiurban area as well as urban area
seeking treatment in the same facility. The information obtained from this study is useful for
the health care providers to evaluate the achievement of cholesterol level and medication
adherence in their own health care setting .

CHAPTER 2

LITERATURE REVIEW

2.1 LDL-C target in Dyslipidaemia and Type 2 Diabetes Mellitus

In Clinical Practice Guidelines on Management of Dyslipidaemia 2011, the

optimal primary target of LDL-C value is dependent upon the patients assessment of global
cardiovascular risk factors(13). NCEP-ATP III recognised three risk group categories and the
LDL-C target is dependent upon to the risks that fall into(14). The three risk groups are low
risk(1 risk factor), moderate risk(>2 risk factors) and high risk category (CHD and CHD risk
equivalents), where in their LDL-C target are <4.1mmol/l, <3.4mmol/l and <2.6mmol/l. The
target for patients with dyslipidaemia and Type 2 Diabetes Mellitus in accordance to NCEPATP III is <2.6mmol/l and this target is similar to the American Diabetes Association(ADA)
(15).

Canadian Diabetes Association(CDA) stated in the 2008 practice guideline that the
LDL-C target for Type 2 Diabetes Mellitus is 2.0mmol/l which is much lower than NCEPATP III(16). European Atherosclerotis Society/ European Society of Cardiology(EAS/ESC)
recommended the primary LDL-C target for patients with very high risk and high risk
as<1.8mmol/l and <2.5mmol/l(17). American College of Cardiology/ American Heart
Association(ACC/AHA) published its latest guideline in 2013 for the treatment of blood
cholesterol to reduce risk of Atherosclerotic Cardiovascular Disease(ASCVD) in adults;
6

raising many controversial issues(18). In the guideline, there is no target of LDL-C and
patients will be treated according to the four statin benefit group. There will be three options
of treatments for these group of patients which encompass high intensity statin, moderate
intensity statin and low intensity statin. Patients with comorbid Dyslipidaemia and Type 2
Diabetes Mellitus will be classified under the group that needs be treated with high intensity
statin(atovastatin 40mg to 80mg or Rosuvastatin 20mg).

2.2 Statin therapy in dyslipidaemia

Statins are the most effective drug class and is the treatment of choice in reducing Low
Density Lipoprotein Cholesterol and they also have an additional effect of antiatherosclerothic
propeties(13, 14, 17). It inhibits 3-Hydroxy-3methyl glutaryl coenzyme A

Reductase

(HMGCoA Reductase) in the liver and limits the rate of hepatic cholesterol synthesis. It is
used as the first line agents in Familial Hypercholesterolemia, primary prevention of
cardiovascular disease, secondary prevention of cardiovascular disease and coronory heart
disease equivalents(13, 19, 20). A natural compound with inhibitory effect towards HMGCoA Reductase was discovered in 1970s by Japanese microbiologist, Akira Endo in a
fermentation broth of Penicillium citrinum during a search for antimicrobial agents(21).
Lovastatin was the first statin to be developed and later followed by simvastatin in 1988,
pravastatin in 1991, fluvastatin in 1994, atorvastatin in 1997 and resuvastatin in 2003. The
mean reduction of LDL-C level with the maximal recommended dose of different statin
ranges from 35% to 55%(14).

Many landmark clinical trials have shown the benefits of statins for primary and
secondary prevention(22-26). These benefits were evident in patients with coronary heart
disease and high or normal blood cholesterol concentrations, as well as in asymptomatic
patients at increased risk of coronary heart disease. The instances of studies conducted
encompassed Scandinavian Simvastatin Survival Study(4S) , Long-term Intervention with
Pravastatin in Ischemic Disease(LIPID), Cholesterol And Recurrent Events trial(CARE),
West of Scotland Coronary Prevention Study(WOSCOPS) and Air Force/Texas coronary
atherosclerosis Prevention Study (AFCAPS/TexCAPS).

In 4S study, 4444 patients with angina pectoris or previous myocardial infarction and
serum cholesterol 5.5-8.0 mmol/L on a lipid-lowering diet were randomised to double-blind
treatment with simvastatin or placebo(23). This study showed that long-term treatment with
simvastatin is safe and improves survival in CHD patients. Sacks et al studied the effect of
pravastatin on coronary events after myocardial infarction in patients with average cholesterol
levels demonstrated that the benefit of cholesterol-lowering therapy extends to the majority of
patients

with

coronary heart

disease

who

have

average

cholesterol

levels(19).

AFCAPS/TexCAPS study was conducted in year 1998 in a healthy individual with average
serum cholesterol level treated with Lovastatin 20-40mg ON(22). The reduction of LDL-C
by 25% was noted and the incidence of first acute major coronory events in men and women
had significantly reduce (183 vs 116 first event;Relative Risk[RR],0.6;95% Confidence
Interval[CI]0.5-0.79;P<0.01)(22).

2.2 LDL-C Achievement and its associated factors

Many studies had been investigating into the LDL-C achievement in patients with
cardiovascular risk factors or patients with cardiovascular disease(27-29). Despite the
effectiveness of lipid lowering agents with specific preference for statin, the results of
attainment of LDL-C by patients varied in each study. A multinational study examined
patients with different risk categories found that a good percentage of patients attained their
LDL-C which in overall was 73%(30). In this study, the researchers also found that most of
the achievers of LDL-C goal attaintment(74%) belong to the low risk category. The predictors
to the success rate were lipid lowering therapy, lower risk group, geographic region, male
gender, older age, race, absence of dietary counselling, diabetes and hypertension(30).

An almost identical study was done by Al-Khateeb et al which looked into the
attaintment of LDL-C among patients with dyslipidaemia in Malaysia(28). They also
discovered that low risk group had achieved their cholesterol target better than the high risk
group and lower baseline LDL-C value was also inversely related to therapeutic goal
attainment(28). The results from the National Cholesterol Education Programme Evaluation
Project Utilizing Novel E Technology II (NEPTUNE II) showed evidence of ethnic
differences in achievement of cholesterol treatment goals(31). NEPTUNE II was conducted
among a group of patients treated with statin therapy which were recorded in the patients
personal medical database. In the study, they concluded that the low achievers in LDL-C goal
attainment among Africans American was due to less aggressive management in this ethnic
group and suboptimal compliance. The other predictors of the treatment success found in this
study were gender, obesity, level of triglycerides, diabetes, high efficacy statin therapy used
and compliance to diet therapy.
9

The undertreatment of LDL-C was investigated in a study done by Pearson et

al. They looked into the awareness among the physicians of the NCEP guidelines and how
well these guideline were being implemented in their clinical practice(32). It was also called
the Lipid Treatment Assessment Project(L-TAP) with the main objective of looking for
utilization of lipid lowering therapy in the primary care practitioners(32). The LDL-C
achievement in patients with coronory heart disease were very low(18%) and researcher
found that the physicians tended not to titrate the dose of statin or use combination therapy.
This was an old study done in 1997 in the era in which potent statin such as atorvastatin was
still unavailable.

An interventional study by Afonso et al evaluated the effectiveness of patient

education programme and provider awareness and the impact toward improvement in LDL-C
attainment(33). This study discovered that only 35.5% of patients achieved their LDL-C
target at baseline which later increased to 59.8% after the intervention programme and 97.3%
of the achievers were patients with higher level of adherence to medication. The subjects
were patients with higher risk for cardiovascular event such as CHD, DM, multiple risk
factors that confer a 10-year risk for coronory artery disease more than 20% or other clinical
forms of atherosclerotic disease(33). The LDL-C target achievers were those in older age
group and who consumed a greater number of medications compared to the nonachievers.

10

2.3 Medication adherence

Compliance, adherence and persistance are the terms that always been used in the
literature to describe the behaviour of medication consumption(34). Currrently, the term
adherence has become a preferred term because it describe the agreement of medication
taking behaviour between patient and physician(35). It is well known that adherence plays an
important role in management of disease to make the treatment productive and yields
satisfactory outcome in the end. Many studies had demonstrated that the causes of the
nonadherence can be due to cost of the drug, side effect of the drug, scepticism towards the
effectiveness of the drug, improved conditionas well as consumption of too many
prescription(36-39).

Nonadherence to medications is common for patients with chronic illnesses such as

cardiovascular disease, diabetes, hypertension and dyslipidaemia. According to the World
Health Organisation, nonadherence with long term medication for conditions such as
hypertension, dyslipidaemia and diabetes is a common problem that leads to compromised
health benefits and serious economic consequences in term of wasted time, money and
uncured disease(40). One review article found the nonadherence toward medication was
41% overall, 36% for antihypertensives, 42% for antidiabetics and 49% for lipid lowering
agents(38). Primary care patients nonadherence to statin medications were evaluated and the
result showed a lower rate of nonadherence which was 37%(41). Another study at different
primary care setting found approximately about 51% patients were not adhered to statin
therapy(42).

11

2.3.1 Measurement of medication adherence

World Health Organization 2003 described adherence as a multidimensional

phenomenon which is determined by five set of factors including socioeconomic factor, health
care system, condition related, therapy related, and patient related(40). Adherence can be
assessed through several different ways. Adherence to medication can be assessed either
through direct methods or indirect method. The examples of direct method are direct observed
therapy, measurement of the level of medicine or metabolite in the blood and measurement of
the biological marker in the blood. The examples of indirect methods are patients
questionnaire / patients self report, rate of prescription refills, pill counts, assessment of the
patients clinical response, electronic medication monitors, measurement of physiologic
markers and patients diaries(43). Systematic review of an article by Vermiere et al found that
direct method is the most accurate method to assess adherence(43).

Measurement level of medicine and markers in blood are the most accurate method but
it is invasive, unacceptable and costly. Direct Observe Therapy is also an accurate method but
it is not practical to be applied to all kind of disease as it involved more human resources and
need patients commitment. Indirect method is more frequently used worldwide especially in
medical research. Interview and all self reported methods are vulnarable to overestimates of
compliance and underestimate of noncompliance(43). Questionnaires and diaries were found
to be moderate to highly concordance to with most of other measure of medication
adherence(44). However, interview based self reporting less likely to be concordance with
nonself report medication adherence(44).

12

The most commonly used in the study are rate of prescription refills (propotion of days
covered (PDC)/ Medication Possesion Rate(MPR ) and 4 or 8 item Morisky Medication
Adherence Scale (MMAS)(35). Prescription refill dates such as Medication Possession
Ratio(MPR) or Medication Refill Adherence(MRA) depends on the completeness of the
pharmacy database and counting tablet given to patients often overestimates compliance(43).
Electronic devices or Medication Event Monitoring System(MEMS) also provide more
accurate method for adherence measurement. This system enables both frequency and times
of opening the medication bootle to be measured(43). MEMS led to discovery of drug
holidays or white coat adherence where the patients adherence pattern correlate with the
time to meet physicians. Despites of presence of various method in measurement medication
adherence, there is still no definite gold standard method(35).

2.3.2 Predictors to poor adherence to medication

Many studies have looked into factors that influenced poor adherence towards
medications. Few major predictors that have been described by various studies include side
effects of medication, presence of cognitive impairment, treatment of asymptomatic disease,
missed appointments, complexity of treatment and poor provider-patients relationship(35).
Richard et al studied the adherence pattern among patients with co-morbid hypertension and
dyslipidaemia. The major predictors for adherence noted in this study were patients who were
initiated with both antihypertensive and antilipid therapy, patients with previous coronory
artery disease or congestive cardiac failure and also patients who took less medication(45).

13

Study by Carol et al looked into the relationship between psychological and cognitive
function with adherence to cholesterol lowering therapy and found that estimated IQ were the
strongest predictors of medication adherence . Mood and personality did not notillustrate any
significant relationship with medication adherence. Likewise, demographic characteristics
such as income and education level in that study were indicated as not significantly related to
medication adherence.

However, Nandini et al described the younger patients between 40 to 54 years old

tendto adhere less to statin therapy compared to patients of 65 years old and (41). The study
also discovered that the patients belief and perceptions towards medications gave an impact
towards the effect of the medication; if the patients believed taking statins lower their risk of
getting heart attacks or strokes, they will adhere better to statin therapy.

2.4 LDL achievement and adherence

National Cholesterol Education Programme(NCEP) has established LDL-C as the
primary target of therapeutic intervention and the target level of LDL-C will be based on
individual cardiovascular risk. In patients with Type 2 Diabetes Mellitus, the recent NCEP
Adult Treatment Panel III guidelines stated that the target level is less than 2.6mmol/l.
Nelia et al studied the achievement of LDL cholesterol level in high risk patients. This
study evaluated the effectiveness of combined intervention targeting the patients and the
providers. The interventions include educating patients regarding their cholesterol level, risk
factors and medication adherence. It is demonstrated that these combined interventions were
successful in improving adherence to medication and at the same time improved the LDL-C
goal attaintment.
14

CHAPTER 3

OBJECTIVES

3.1 General Objectives

To determine the proportion of achievement of low density lipoprotein cholesterol target, the
associated factors to nonachievement of LDL-C target and adherence to statin therapy among
patients with Type 2 Diabetes Mellitus.

3.2 Specific objectives

1.

To determine the proportion of low density lipoprotein cholesterol target level

achievers and nonachievers among patients with Type 2 Diabetes Mellitus.

2.

To determine the patients adherence to statin therapy among patients with Type 2

Diabetes Mellitus.
3.

To determine the

associated factors to nonachievement of LDL-C target among

patients with Type 2 Diabetes Mellitus.

3.3

RESEARCH HYPOTHESIS

Sociodemographic and clinical factors are associated with the nonachievement of LDL-C
target.

15

3.4

Operational definition

1. Low density lipoprotein cholesterol(LDL-C) achievement is based on the National

Cholesterol Education Programme Adult Treatment Panel III. This study only measured the
general LDL-C target for patients with Type 2 Diabetes Mellitus in accordance to the
guideline which is less than 2.6mmol/l. The achievers for LDL-C target are grouped as
below:
(i) LDL-C target achievers = diabetic patients who attained LDL-C level < 2.6mmol/l
(ii)LDL-C target nonachievers = diabetic patients who attained LDL-C level 2.6mmol/l

2. A patient is considered to adhering to medication if he/she scored a total percentage of

75% in Medication Compliance Questionnaire. We devided the category of adherence in
our study as below:
iiiiii-

Fully adhered: patients who attained 100% score in MCQ

Adhered: patients who attained 75% score in MCQ
Nonadhered: patients who attained <75% score in MCQ

16

CHAPTER 4
METHODOLOGY

4.1 Study design

This is a cross sectional study.

4.2 Study area

This study was conducted in Klinik Rawatan Keluarga(KRK), Hospital Universiti
Sains Malaysia(HUSM) which is situated in Kubang Kerian, Kelantan. HUSM also a centre
for referral for whole state of Kelantan. Klinik Rawatan Keluarga is an outpatient clinic and is
run by 50 staffs including the Family Medicine Lecturers, the Family Medicine Specialist in
training, medical officers and nurses. Daily attendance in KRK ranges from 200 to 300
patients. KRK is an integrated clinic and Diabetes Mellitus was one of the major chronic
illness who visit KRK.

4.3 Population and sample

4.3.1 Reference population

Reference population was the patients with Type 2 Diabetes Mellitus in Kelantan.

17

4.3.2 Source population

Source population was the patients with Type 2 Diabetes Mellitus attending Klinik
Rawatan Keluarga in Hospital Universiti Sains Malaysia.

4.3.3 Study population

Patients with Type 2 Diabetes Mellitus who attended Klinik Rawatan Keluarga in
Hospital Universiti Sains Malaysia from January 2013 to May 2013 and fulfilled the inclusion
and exclusion criteria.

4.3.4 Inclusion criteria

1. Age 18 years old and above.
2. Patient diagnosed with Type 2 Diabetes Mellitus.
3. Patient diagnosed with Dyslipidaemia.
4. Duration of undergoing statin therapy were more than 6 months.

4.3.5 Exclusion Criteria

1. Patient with psychiatric illness or mental retardation.
2. Unable to read or write.
3. Triglycerides > 4.3mmol/l

18

4.3.6 Sampling method

Systematic random sampling in the ratio 1:2 based on patient attendance list for blood taking in
KRK.

4.3.7 Sample size calculation

Sample size was calculated for all the objectives. However, the one that yield the biggest number
was taken as the sample size. The probability of non-respond, drop out or missing data was 30%.

Objective 1: To determine the proportion of low density lipoprotein cholesterol target level
achievers and nonachievers among patients with Type 2 Diabetes Mellitus.
Calculation of sample size using formula single proportion.
n = ( z / ) p ( 1 p )
n = minimum required sample size
z = value of standard normal distribution = 1.96
= absolute precision = 0.07
p = anticipated proportion of LDL-C achievers from Parris et al =44%(46)
p = 0.44
n= 193
n + 30% drop off = 251
The minimum sample size calculation is 193 and after considering 30% non
respondent, the sample size is 251.

19

Objective 2: To determine the patients adherence toward statin therapy among patients with
Type 2 Diabetes Mellitus.
Calculation of sample using formula single proportion.
n = ( z / ) p ( 1 p )
n = minimum required sample size
z = value of standard normal distribution = 1.96
= absolute precision = 0.07
p = anticipated proportion of adherence to statin from Nandini et al =37%(41)
p = 0.37
n=180
n+30% drop off =234
The minimum sample size calculation is 180 and after considering 30% of the non
respondent, the sample size is 234.

Objective 3: To determine the associated factors to nonachievement of LDL-C target among

patients with Type 2 Diabetes Mellitus.
Categorical variables
The sample size calculation was done using Power and Sample Size Calculation software. The
sample size for categorical variables was calculated by comparing two proportions formula. The
calculation of sample size was as follows:

20

Level of significant = 0.05

Power

0.8

0.47(Proportion of LDL achievers among male patients)(42)

P1

0.67 (expected proportion of LDL nonachievers among male patients)

m=1

The sample size shown by the PS Software= 95, Therefore the final number of sample requirred is
95(1+1) =190. After considering the non-respond rate of 30%, the number of patients needed in
this study was 247.
Numerical variables

The formula of comparing two means was used to calculate the sample size for numerical
variables. The calculation of the sample size was as follows:

= 0.05

Power

=0.8

= 9.2(standard deviation of mean age in LDL-C nonachievers)(42)

= 5(expected detectable difference mean age LDL-C achievers and LDL-C

nonachievers)

Sample size by shown by PS Software= 54, Therefore the final number of sample requirred is
54(1+1) =108. After considering the non-respond rate of 30%, the number of patients needed in
this study was 140.

21

Table 4.1 Sample size culculation for categorical variables

Variables

P0

P1

Minimum
size(n)

sample n+30%
rate

Gender(42)

0.47

0.67

190

247

Adherence group(42)

0.59

0.39

194

252

nonrespond

Table 4.2 Sample size culculation for numerical variables

Variables

Age

9.2

Minimum
size(n)
108

sample n+30%
rate
140

BMI

3.6

104

135

SBP

19.6

10

122

158

DBP

12

190

247

nonrespond

The biggest sample size belongs to objective 3 which was 252. In this study, the sample size
of 252 was used.

22

4.4 Research tools

The research tools consisted of:
1) Case report Form. This section was filled up by interviewer.

a. Socio demographic data consists of information regarding age; sex; race; marital status;
smoking status; occupation; income and education level.
b. Clinical data information including medications (number of medications and type of
statin), investigations result (lipid profile and HbA1c) and examinations (weight,
height and blood pressure).
2) Self administered questionnaires. This section was filled up by study subjects.
a. Patients treatment data which includes information about the duration anticholesterol
medication consumption, knowledge and side effects of anticholesterol medication
consumed.
b. Medication adherence questionnaire: Medication Compliance Questionnaire(MCQ) was

used in this study. It was developed by Hassan et al in 2006 to assess adherence

towards antihypertensive medication(47). It is comprised of a set of 10 questions
which consists of 2 domains: a drug taking behaviour domain comprising 7 items and
a drug stopping behaviour domain comprising 3 items . The internal consistency
realibilities (cronbach alpha) were 0.67 and 0.84 and test-retest single measure
intraclass correlation coefficient were 0.78 and 0.83. The scores are calculated using
the Likert scale ranging from 1 to 5 with 1 indicating never and 5 indicating very
frequent. All negatively worded scores were reversed and all scores were converted to
0 to 100 score. Patient with good compliance or adherence with a score of

75%

correspond with frequently and very frequently for all item in the questionnaire.
Patients who score < 75% considered to be in the nonadherence group. Fully adhered
group were those patients who score 100%.
23

Pretest of questionnaires: the pretest of the questionnaire was conducted among 10

patients with T2DM on statin therapy attended Klinik Pakar Perubatan, HUSM. The
clarity and appropriateness of questions was analyzed. It took about 10 minutes to 15
minutes for each respondant to complete the set of question.
3) HUSM Online medical record database: Patients treatment information and blood result
were gathered from an online record database. Clinical data contains information
regarding medication taken; blood investigation results including cholesterol level and
HbA1c level .

4) Weighing scale, measuring tape and OMRON digital sphygmanometer were used for the
measurement of weight, height and blood pressure; the examination tools had been
calibrated as scheduled and the same tools were used during the period of the study.

5)

Laboratory machine that had been used to analyze blood cholesterol result and HbA1c result
were Chemical Analyzer: Archtect C800 and HbA1c Analyzer:Biorad. These machines are
used in HUSM laboratories and calibration were done as scheduled.

24

4.5 Data collection procedure

Patients with Type 2 Diabetes Mellitus who attended KRK for current routine blood
investigation during the period of this study were selected using systematic random sampling
1 in 2 using the attendance list. Patients with Type 2 Diabetes Mellitus who fulfill the
inclusion and exclusion criteria were included in the study. Eligible study subjects were
given information and explanation regarding the study. Subjects with consent signed the
consent form and were interviewed. Patients were then given self administered and validated
compliance questionnaire to complete
The researcher completed the remaining information needed with the data taken from
the patients online medical record. For each subject of the study, the online blood result and
list of medications taken were traced by keying in the patients hospital registration number
in the online result database

and online prescription database. The result of blood

investigations (lipid profile and HbA1c) were taken from the test done on the day of the
interview. If the blood results were not available and Trygliceride result shows a level of
more than 4.3mmol/l, the subjects were excluded from the study.

4.5 Statistical analysis

Data entry and analysis was done using Statistical Package for Social Sciences (SPSS)
version 22. Descriptive statistics was used to analyze the socio-demographic and clinical data.
The distribution and frequencies were examined. All numerical variables were expressed as mean
and 95% confident interval. Frequency and percentage were calculated for categorical variables.

Objectives 1 to 2 were also analyzed using descriptive statistics. For objective 3, the
associated factors were analyzed by multiple logistic regression. The significant p value was
set at <0.05 with 95% confidence interval.
25

4.5.1 The procedure of multiple logistic regression

The distribution and frequencies were examined. All numerical variables were
expressed as mean and 95% confident interval. Frequency and percentage were calculated for
categorical variables. Bivariate analyses were performed to determine which independent
variables were associated with nonachievement of LDL-C target. Variables with p value <0.25 in
bivariate models and clinically significant variables were then included in the multivariate logistic
models. This p value was set larger than the level of significance to allow more important
variables to be included. Backward and forward methods were used for the selection of variables.
In addition, interaction terms between variables, based on behavioral or biologic
plausibility were accounted for to assess their significance to the multivariate models. Significant
interactions were retained in the final model. Multicollinearity and interaction was not checked
since there was only one significant variable noted from the multiple logistic regressions. Then,
preliminary final model was obtained.
The fitness of the model was tested by Hosmer and Lemeshow goodness of fit test. The
model is perfectly fit if the p value approaches to one. The classification table and receiver
operating characteristic (ROC) curve was also used to determine the fitness of the model.

4.6 Ethical consideration

The proposal of this study was presented to the Department of Family Medicine and Ethics
Committee of University Sains Malaysia. Ethical approval was received on 8 April 2012.
(Appendix I).

26

Figure 4.1 Flow chart of the study

REFERENCE POPULATION
Patients with Type 2 Diabetes Mellitus on statin therapy in
Kelantan

SOURCE POPULATION
Patient with Type 2 Diabetes Mellitus on statin therapy
attending Klinik Rawatan Keluarga, HUSM

SELECTION

SAMPLING METHOD

Inclusion and exclusion critrteria

Systematic Random Sampling

RESEARCH TOOLS
Self administered questionnaires/Case Report
Form:
sociodemography data, patients treatment, Medication
Compliance Questionnaires
Online database record:prescription/laboratory
result
Examination tools:spygmanometer, weighing
scale, measuring tape,
DATA ENTRY AND ANALYSIS

27

Figure 4.2 Conceptual framework of study

ADHERENCE

-comply to treatment
-multidimension( socio-economic, health care system, condition related, patient related, therapy relate

Medication

Social factors
-assessibility to health care centre
-education
- household income

-lipid lowering therapy

-type
-duration
-polypharmacy
LDL-C target achievement in T2DM
(NECP-ATP III)
Nonmodifiable risk factors
-age
-gender
-race

Concurrent disease control:

Hypertension
Diabetes
Obesity
Behaviour: Smoking cessation

LDL-C target achievers

<2.6mmol/l
LDL-C target nonarchievers
2.6mmol/l

28

CHAPTER 5
RESULT

A total of 234 diabetic patients with underlying dyslipidaemia attended Klinik Rawatan
Keluarga were eligible and participated in the study. The response rate was 92.8%.

5.1 Socio-demographic characteristic of respondents

The mean age of the respondents was 59.2(9.21) years old.. The male and female
respondents involved were almost equal in number. Majority of the respondents were Malay.
More than half of the respondents(65.8%) completed their secondary school. The sociodemographic characteristics of respondents were shown in Table 5.1.

Table 5.1 : Socio-demographic characteristic of respondents.

Variables

meanSD

Age (YearsSD)

59.29.21

Distribution
of Percentages(%)
respondents (n=234)

Sex
Male

103

44.0

Female

131

56.0

Malay

213

91

Others

11

Married

209

89.3

Unmarried /widow

25

10.7

Race

Marital status

29

Continue Table 5.1

Education
Primary

52

22.3

Secondary

154

65.8

Tertiary

28

12.0

RM700

116

49.6

>RM700

118

50.4

Income

5.2 Clinical characteristics of respondants

Majority of respondents were nonsmoker(96%). Majority

of the respondents were

prescribed with a total of 4 or more types of medications and Atorvastatin was the most
common statin prescribed(68.8%). Half of the respondents(50.4%) were already on statin for
1 to 5 years. However most of the respondents did not experience any side effects of statin
therapy(89.7%). The mean BMI, SBP, DBP, HbA1c and LDL were 26.4(5.30) kg/m 2 ,
134.11(16.18) mmHg, 81.21(9.68) mmHg, 7.92(1.90) % and 2.96(0.96) mmol/l respectively.
The clinical characteristics of respondents were shown in table 5.2.

30

Table 5.2: Clinical characteristics of respondants

Variables

MeanSD

Distribution of respondents
(n=234)

Percentages(%)

Smoker

3.8

Nonsmoker

225

96.2

52

22.2

182

77.8

88

37.6

146

62.4

Smoking status

Number of
prescribed
medications
<4
4

Weight(kg)

66.514.13

Height(cm)

158.47.57

BMI(kg/m2)

26.45.30

Systolic BP

134.1116.18

(mmHg)
Diastolic
BP(mmHg)

81.219.68

HbA1c(%)

7.921.90

Total
Cholesterol(mmol/l)

4.891.13

LDL(mmol/l)
<2.6
2.6
Triglyceride
HDL

2.960.96

1.650.73
1.230.26

Continue Table 5.2

Duration on statin
31

6mth to 1 yr

49

20.9

1 yr to 5yr

118

50.4

More than 5 yr

67

28.6

Lovastatin

10

4.3

Simvastatin

45

19.2

Atorvastatin

161

68.8

Pravastatin

18

7.7

Yes

49

20.9

No

185

79.1

Yes

56

23.5

No

178

76.5

No side effect

210

89.7

GI upset

15

6.4

myalgia

1.3

Others

2.5

Types of statin

Knowledge of type
of statin taken

Knowledge of dose
of statin taken

Side effect
experienced by
patients

32

5.3 Proportion of LDL-C goal achievers and nonachievers

The proportion of LDL goal achievers and nonachievers among patients with Type 2
Diabetis Mellitus

on statin therapy attending Klinik Rawatan Keluarga, HUSM was

illustrated in figure 5.1.

Figure 5.1: The proportion of LDL cholesterol achievement among patients with Type 2
Diabetes Mellitus.

37.6

62.4
Achievers(LDL<2.6mmol/l)

Nonachievers(LDL2.6mmol/l

33

5.4 Percentage of adherence to statin therapy

The percentage of patients with Type 2 Diabetes Mellitus in adherence to statin therapy was
illustrated in figure 5.2.
Figure 5.2 : The percentage of patients with Type 2 Diabetes Mellitus in adherence to statin
therapy

48

Fully adhered
Adhered
Nonadhered

182

34

5.5 The associated factors to nonachievement of LDL-C

target among patients with Type 2 Diabetes Mellitus

5.5.1 The associated factors to nonachievement of LDL-C target

by Simple Logistic regression
The screening for sociodemographic and clinical factors was performed through simple
logistic regression. Age, BMI, SBP, HbA1c and patientss knowledge of dose of statin taken
are at the p value < 0.25. The variables with a p value of <0.25 and clinically or biologically
significant variables were included for further analysis in Multiple Logistic Regression. The
results of simple logistic regression were shown in table 5.5.1 and table 5.5.2.

Table 5.3: Association between sociodemographic factors and nonachievers of LDL-C target
screening by Simple Logistic Regression.
Sociodemographic

Regression

variables

coefficient

Age (year)
Sex
Male
Female

Crude OR (95%CI)

Wald statistic

p
value

-0.026

0.97(0.95-1.00)

3.005

0.083

0.167

1.00
1.18(0.69-2.01)

0.379

0.538

0.031

0.861

0.179

0.672

Marital status
Married
Unmarried /widow
Race
Malay
Continue
Table 5.3
Nonmalay

1.00
0.077

1.08(0.46-2.56)
1.00

0.205

1.23(0.48-3.17)

Education
35

Continue Table 5.3

No formal
education
Primary

1.00

2.940

0.401

0.262

1.30(0.24-7.14)

0.091

0.763

Secondary

0.674

1.96(0.38-10.06)

0.652

0.419

Tertiary

0.143

1.15(0.20-6.74)

0.025

0.874

0.501

0.479

Income
RM700
>RM700

1.00
-0.191

0.83(0.49-1.40)

Table 5.4: Association between clinical data and nonachievers of LDL-C target screening by
Simple Logistic Regression
Clinical variables

Regression

Crude OR (95%CI)

Wald statistic

p value

1.00

0.073

0.788

0.255

0.614

coefficient
Smoking status
Nonsmoker
Smoker

0.194

1.21(0.30-4.98)

Number of prescribed
medications
<4

1.00

-0.166

0.85(0.45-1.61)

BMI

-0.039

0.96(0.92-1.01)

2.389

0.122

SBP

-0.015

0.99(0.97-1.00)

3.277

0.070

DBP

-0.007

0.993(0.96-1.02)

0.252

0.616

HbA1c

0.236

1.27(1.08-1.49)

8.227

0.004

36

Duration on statin
6mth to 1 yr

1.00

0.938

0.626

1 yr to 5 yr

0.173

1.19(0.60-2.37)

0.244

0.621

More than 5yr

-0.125

0.88(0.42-1.87)

0.107

0.744

Knowledge of type of

0.394

statin taken
No

1.00

Yes
Knowledge of dose of

-0.278

0.76(0.40-1.42)

0.726

statin taken

0.092

No

1.00

Yes

-0.526

0.591(0.32-1.09)

2.832

1.00

2.485

0.448

Types of statin
Lovastatin
Simvastatin

0.405

1.500(0.38-5.94)

0.334

0.563

Atorvastatin

0.494

1.639(0.456-5.89)

0.573

0.449

Pravastatin

1.253

3.500(0.66-18.50)

2.175

0.140

1.00

4.030

0.133

Adherence to statin
therapy
Fully adhered
Adhered

0.636

1.89(0.99-3.59)

3.759

0.053

Nonadhered

1.099

3.00(0.29-30.90)

0.852

0.356

5.5.2 The Associated factors to nonachievement of LDL-C target

by Multiple Logistic Regression

The only significant factor associated with nonachievers of LDL-C target was the
HbA1c level when the confounders were being controlled(Table 5.5).
37

Table 5.5: Associated factors to nonachievement of LDL-C target by Multiple Logistic

Regression
Variables
HbA1c

Regression

Adjusted OR

coefficient

(95%CI)

0.236

1.266
(1.08-1.49)

Wald statistic
(df)

P value

8.227
(1)

0.004

Forward LR Multiple Logistic Regression was applied

The interaction and multicollinearity were not proceeded accounting that only one factor was
significant.

Model fitness was checked by Hosmer Lemeshow goodness-of-fit test, classification table and
area under ROC (Receiver Operating Characteristics) curve. The p value for Hosmer
Lemeshow goodness-of-fit test was not significant(p=0.264). The classification table showed
that 65.4% of cases were predicted correctly whether they were nonachievers or achievers of
LDL-C target. The area under the curve of ROC was 0.606. The model can accurately
discriminate 60.6% of the cases (it is significant to discriminate more than half of cases). The
The preliminary model was accepted for the final model based on Hosmer Lemeshow
goodness-of-fit test and ROC curve as classification table did not produce a good value.

Interpretation of Multiple Logistic Regression

A patient with Type 2 Diabetes Mellitus who had an increase 1% of HbA1c has 1.3 times the
odd to become nonachievers LDL-C target (95% CI 1.08,1.49,p<0.05).
38

Therefore, 1% increment of HbA1c level will increase the chance of patient with Type 2
diabetes Mellitus to become nonachievers of LDL-C target by 1.3.

39

CHAPTER 6
DISCUSSION

6.1 Proportion of LDL-C goal achievers and nonachievers

among patients with Type 2 Diabetes Mellitus

This study revealed that the LDL-C goal achievers among patients with Type 2
Diabetes Mellitus were 37.6%. It is not a shocking result as this percentage was almost similar
with the figure from National Diabetes Registry (NDR) that was conducted from 2009 to
2012 at primary care clinics in Malaysia which yield the result of 37.8%(48). NDR was an
initiative of the Malaysia Ministry of Health in evaluating the target achievement and clinical
outcomes in patients with diabetes who were managed at primary health care clinics.
However, the subjects studied by the NDR shared the same characteristics of subject studied
such as underlying Diabetes Mellitus, similarities in ethnicity and geographical region.

Mafauzy et al conducted a DiabCare Malaysia 2008 project and assessed the

management of diabetes in general hospital, diabetes clinic and referral clinic throughout the
country. They discovered that 46% diabetic patients had LDL-C > 2.6mmol/l(49). Both
DiabCare 2008 and NDR represent performance of LDL-C target achievement for whole
states in Malaysia. Another published local diabetic audit which by was conducted by Shariff
et al in two urban public primary care clinics in Malaysia revealed a very low LDL-C target
achievement which was 13.0%(50). From these results, we can conclude that the range of
LDL-C target achievement in Malaysia is between 13% to 46%.
40

Globally the trend of LDL-C goal achievement ranges from 18% to 73% but there
were differences in the popualation group studied(28, 30, 32, 33). However, our finding
showed a lower percentage compared to a large multinational patient population study
involving 9 countries which illustrated the percentage of 67% , 74% and 86% achievement of
LDL-C in high risk, moderate risk and low risk patients(51). The target of LDL-C was based
on the NCEP-ATP III recommendation. The study also included various form of lipid
lowering therapy but almost 75% of the subjects were on statin therapy and atorvastatin was
the most commonly used as in that study. We also noted that in our study, more than half of
the subjects(68.8%) was on atorvastatin. The percentage of achievement of LDL-C was
doubled in the high risk group in comparison to our study. The countries that involved in the
study were the United States of America, Canada, France, Netherlands, Spain, Brazil, Mexico
and two representative from Asian countries including Korea and Taiwan. They also found
that European countries exhibited higher achievement rate in moderate to high risk group and
the other countries illustrated a higher percentage in the low risk group.

On the contrary, another study conducted at the institution similar to our study found
an overall LDL-C reaching goal was 64.2% and 50.5% from them were in the high risk
group(28). However, the study did not focus on one homogenous disease as we did in our
study. In our study, we included subjects with diabetes mellitus and dyslipidaemia to
investigate how well this group of patients achieve their LDL-C level despite being on statin
therapy.

Kauffman et al recruited more than 7000 patients with coronary artery disease and
looked into the achievement with a lower target of 1.8mmol/l in accordance with the NCEP
41

guideline which revealed about 43.4% of patients achieving their LDL-C target(27). They
found that even in a good health care system and a dedicated team treating dyslipidamia there
were still difficulties in getting the majority of patients to achieve the target. In the study, the
patients received statin monotherapy, nonstatin therapy and combination lipid lowering
therapy and the result showed that the majority(92.4%) of the LDL goal achievers were
receiving statin monotherapy or in combination.

Since our study was conducted among patients with a high risk for cardiovascular
disease, we expected that the percentage of patients achieving the LDL-C target would be
higher as most of the previous studies showed better achievement of the LDL-C target
compared to the patients in the low to moderate risk groups.

6.2 Percentage

of

adherence

to

statin

therapy

and

relationship with
LDL-C target achievement

We reported a high rate of adherence to statin therapy which was 98.3%. About 20.5% of
the patients were adhering fully(100% score of MCQ) and 77.8% of the patients were
adhering (75%). It reflected that our population had a better adherence rate to lipid lowering
therapy compared to other treatment of chronic illnesses such as diabetes or hypertension.
This study revealed a very low nonadherence rate to statin therapy at 1.7% among
patients with dyslipidaemia and Type 2 Diabetes Mellitus who had attended KRK, HUSM.
42

This figure was extremely low compared to other studies that which recorded the
nonadherence rate at 37% to 51%(38, 41, 42). The possibilities of such result could be due to
the different method or tools administered in assessing adherence, misunderstanding during
answering the self administered questionnaire and our subjects having good adherence to
statin therapy. Interview and all self reported methods are vulnarable to overestimates of
compliance and underestimate of noncompliance(43).
A review of article by Cramer et al regarding compliance and persistance in the treatment
of diabetes, hypertension and dyslipidaemia showed that Medication Possession Ratio(MPR)
was the commonly used method(38). Most of the studies on adherence to medication used
simpler questionnaire such as MMAS with answer options of yes or no (37, 39, 42, 52). Our
study used a validated Medication Compliance Questionnaires was previously used in
compliance to antihypertensive and oral hypoglycaemic agent(47). This questionnaire is more
complex compared to MMAS because it contains 10 items and patient need to choose
suitable answers in the form of Likert scale(never, seldom, sometimes, frequent and very
frequent) but theoritically it will yield a more accurate adherence result. A study did a
comparison between the Likert scale and traditional measures of self efficacy and the results
indicated that Likert-type and traditional measures of self-efficacy have a similar reliability
error variance, provide equivalent levels of prediction, and have similar factor structure and
similar discriminability(53). Questionnaires are easy to be used but can be susceptible to
misrepresentation and tends to cause the health care providers to overestimate the patients
adherence(35). The use of medication questionnaire scale was compared to pharmacy fills rate
and they found that the concordance was 75% and MMAS significantly associated with
pharmacy refill adherence(54).
However, there were no gold standard established in assessing patients adherence to
medications(35). The decision to choose the method of assessing adherence is dependent

43

upon the researcher and by accounting for the factors such as accuracy, avaibility, simplicity,
advantages and appopriateness.
Bermingham et al had administered the MMAS adherence questionnaire and reported that
59.2% of LDL-C achievers were fully adhered and 39.6% of LDL-C nonachievers were fully
adhered. In our study, both LDL-C achievers and LDL-C nonachievers had an equal
percentage of patients that were adhering fully to statin therapy. The adherence of patients did
not reveal any significant difference to the LDL-C

achievement. However, prospective

analysis of LDL-C goal achievement among statin user in the primary care revealed that the
factor most associated with LDL-C target achievement was MMAS score(42).
Hassan et al had validated Medication Compliance Questionnaire(MCQ) and assessed the
compliance of patients toward antihypertensive medication(47). MCQ revealed 55.8% of
patients not adhered to the medication. However, the used of similar tool in this study
reported a high adherence rate. The higher adherence rate in our sample even though using
similar tool could be because of simpler dosing of statin compared to antihypertensives which
can be given as twice even trice daily.
According to Casula et al, adverse effects of the statin was one of the important cause of
nonadherence. They reported that 30% to 62% discontinuation of statin therapy was due to the
side effects of statin(55). In our study, 10.2% of respondents had experience side effects of
statin and 3.8% of respondents had had history of discontinuing statin due to its side effects.
The low incidence of side effects among these patients could contribute to the high adherence
rate among these patients.

44

6.3 The associated factors to nonachievement of LDL-C

target
6.3.1 Sociodemographic factors
To our suprise, all result of the sociodemographic variables tested in our study turned
out negative. This study revealed that age, gender, marital status, education level and
household income did not have any association to the non achievement of the LDL-C target.
This finding was in contrary to the previous study that evidently showed the
sociodemographic variables as important predictors for LDL-C achievement(27, 30-32, 56).
Waters et al posited that geographical region(p<0.0001), male gender(p<0.0001), older
age(p<0.0001) and race(Asian>white>black;p<0.0001) were predictors for successful LDL-C
goal achievement(30). Clark et al analyzed the result from the NEPTUNE II and looked into
the ethnic differences in the achievement of the cholesterol treatment goal. They found that
African American had a lower success rate in achieving the LDL-C target compared to Non
Hispanic White. Kauffman et al evaluated the LDL-C achievement among patients with
coronory artery disease and their result illustrated a similar finding that the likelihood of older
patients and men patients to attain the goal were more significant.

Our study was in concordance with the study done by Bermingham et al where in it
was discovered that age and gender factors were not associated with the achievement of LDLC goal. Another study which scrutinized the LDL-C achievement in patient with peripheral
arterial disease found that these patients were more likely to achieve the target when they get
older and have coronory artery disease(57).

45

In the study by Kauffman et al , a number of differences were noted; the

characteristics include Chronic Disease Score(CDS), age, sex, BMI, highest level of LDL-C
recorded, a diabetes mellitus, congestive heart disease, gout, hypertension and count of
coronory artery disease risk factors(27).

This is the only study that has noted many

differences in both achievers and nonachievers group possibly due to the huge number of
subjects. Lipid Treatment Assessment Project (LTAP) reported a large proportion(62%) of
dyslipidemic patients in the United States who are being treated in a primary care setting are
not achieving the NCEP target LDL-C level(32). Those at highest CHD risk are least likely to
reach the target LDL-C level African-Americans are less likely than Whites or Hispanics to
achieve these goals.(32).

Afonso et al noted that the LDL-C target achievers were significantly older than
nonachievers (p=0.02)(33). The mean age for LDL-C achievers

in our study was

60.6(SD8.64) vs 58.4(SD9.47);p=0.081. Kauffman et al also illustrated the significant

difference in the age (p=0.001). However, most of existing studies failed to show similar
result(27, 32, 42). A study by Bermingham et al in primary care clinics also showed no
significant differences in age, SBP, DBP and BMI but they noticed a significant difference in
adherence to drug therapy in both groups. The average score for adherence using MMAS was
lower in nonachievers group (3.0(SD0.99) vs 3.4(SD0.93);p=0.029) (42).

6.3.2 Clinical factors

The result of this study suggests that only significant factor that is associated with
nonachievement of LDL-C target was HbA1c(Adusted OR1.3 (95% CI 1.08,1.49,p<0.05).

46

The result of our study showed that an increment of 1% of the HbA1c level will increase the
chance of patient with dyslipidaemia and Type 2 diabetes Mellitus to become nonachievers of
LDL-C target.

We found few studies described the association of HbA1c with LDL-C level(11, 5861). Our study confirmed previous findings that HbA1c as a predictor marker for cholesterol
level(59, 61). Khan et al clearly demonstrated in their study that HbA1c had a direct and
significant correlation with cholesterol, triglycerides, LDL-C and inverse correlation with
HDL(61). They studied both female and male diabetic patients but the finding showed that the
result had no differences in term of gender. Similar findings also had been described in our
study. Wagner et al looked into the effect of improving glycaemic control on LDL-C particle
sizes in diabetic patients and found the favourable effect of improving glycaemic control on
lipid and lipoprotein(11). They concluded that glycaemic optimization is a good tool to
improve the component of diabetic dyslipidaemia(11).

VinodMahoto et al also described similar association between glycaemic control and

serum lipid profile in patients with Type 2 Diabetis Mellitus(59). In that study, the diagnostic
value of HbA1c was evaluated and they found the value HbA1c value >7.0% had
significantly higher value of LDL-C as compared to patients with HbA1c 7.0%(59). A
slightly different finding which was found in that study was total cholesterol and LDL-C
significantly higher(p<0.05) in female patients(59). Singh et al studied the relationship of
HbA1c and lipid profile in Pujnabi Type 2 diabetic population(60). They found HbA1c was
positively and significantly related with total cholesterol, HDL and very LDL(60). However,
inconsistent with the finding from previous study was LDL-C did not show any significant
relation with HbA1c.
47

As LDL-C cannot be measured in certain circumstances (such as triglycerides >4.3),

Nirajan et al observed a significant correlation between glycaemic control and lipid ratio
including triglyceride/HDL ratio, total cholesterol/HDL ratio and LDL/HDL ratio(58).
Triglyceride/HDL ratio is also a known indicator of LDL-C particle size and is used as an
alternative target when LDL-C cannot be measured(13).

Our study and previous studies had a similar conclusion that HbA1c has a dual
biomaker capacity where as a glycaemic control as well as a LDL-C indicator(59, 61, 62).
We think that patient with better glycaemic control would adhere better to medication and
therapeutic lifestlye. Both of this condition would contribute to better control of other target in
diabetes such as cholesterol level. Biochemically, the explanation of relation between HbA1c
and lipid profile was described by several studies. Lipoprotein metabolisms in T2DM patients
are altered in several ways. Insulin stimulates lipoprotein lipase activity. Patients with T2DM
who exhibit both insulin deficiency and insulin resistance had reduce in lippoprotein lipase
activity(63). Hyperglycaemia with moderate to severe intensity has decrease rate of clearance
for LDL apoprotein B(63). LDL-C binding to the receptor at endothelium of the vessel also
reduce in T2DM as it was stimulated by insulin. Apart from that, insulin inhibit the human
sensitive activity and leading to the increase production of free fatty acid from triglyceride.
Peters et al described that presence of abnormal triglycerides metabolism and/or lipid transfer
activity leading to alteration of lipoprotein composition(64). In another study, lipid
peroxidation reported to be increased in especially in uncontrolled diabetic or hyperglycaemia
and altered lipid metabolism(65).

Davidson et al analyzed the NEPTUNE II in terms of it implication of treatment and

achievement of the LDL-C target. The major predictors for successful treatment found in this
48

study were the presence of three or more major coronory heart disease risk factors(p=0.003)
and ranging between age 45years in men or 55years in women. In contrast, patients who
were current smokers(p=0.0002) and patients with triglycerides 2.25mmol/l(p<0.0001) were
less likely to achieve their LDL-C target(20).

Schectman et al evaluated the factors that restricting the LDL-C target achievement in
patients with cardiovascular disease which showed that the predictors of LDL-C achievement
were lower baseline LDL-C tryglycerides, the use of combination of drug therapy rather than
monotherapy and patients adherence to treatment(66). This was an existing study in 1996 and
the more potent statin such as atorvastatin was still not available. In our study, we
administered a crossectional study and did not evaluate the characteristic of the baseline and
the patients were on monotherapy statin treatment.

Andrews et al made a comparison between different types of statin including

atorvastatin, simvastatin, pravastatin, fluvastatin and lovastatin. The LDL-C level was elicited
at baseline and after 54 consecutive weeks of treatment; the dose of each statin was titrated
accordingly. The greatest mean reduction of LDL-C was elicited among patients on
atorvastatin. The percentage reduction in LDL-C achieved at an initial dose correlated
strongly with the proportion of patients who maintained their goals at 54 weeks(r=-0.84)(67).
In our study, the association between the type of statin used and the LDL-C achievement was
analyzed. There was no significant association noted. The possible reason postulated was that
it is probable that most of the patients had started on statin therapy in accordance to statin
reduction percentage. Even with different types of statin used; provided that the dose the dose
is initiated in accordance to the percentage reduction of LDL-C, it will produce a significant
LDL-C reduction.
49

CHAPTER 7

CONCLUSIONS

Achievement of Low Density Lipoprotein target in Type 2 Diabetes Mellitus with

dyslipidaemia among patients who attended KRK,HUSM was still low(37.6%) even with the
availability of potent statin therapy. Majority of the patients(98.2%) adhered to statin therapy
and 20.5% of the patients were full in adherence. However, there were no association between
adherence and LDL-C achievement. In this study, HbA1c was the only significant factor
associated with nonachievement LDL-C target.

50

CHAPTER 8

LIMITATIONS OF THE STUDY

This study has been designed with our paramount ability in order to get valid data and reliable
results. However, similar to any other studies, this study is not exempted from limitations as
outlined below:

1. The major factors that can influence cholesterol level such as dietery pattern and
physical activity are not assessed in this study. This study only explored the
sociodemographic and clinical factors.
2. The diagnosis of Type 2 Diabetes Mellitus and Dyslipidaemia was based on self
report. There will be bias; regardless if a proper diagnosis is made according to the
relevant guideline.

3. This study did not evaluate the co-morbidities and other risk factors as been described
in previous study. We only looked into patients with Type 2 Diabetes Mellitus and
Dyslipidaemia.

4.

The data represents only one outpatient clinic in tertiary centre, instead of involving
other outpatient clinics in other tertiary centre or other primary health clinic in other
districts or states. Therefore, the results of the study are not representative of entire
population.
51

5. The study has limitation in term of its design and sampling. It was a cross-sectional
study and the selection of participants were done by accounting only the patients who
attended the clinic for blood taking procedure which might lead to the bias in the
recruitement of the patients.
6. This study used a self-reported measurement of adherence which might be over or
underreported. Therefore, the actual proportion of non-adherence to statin therapy may
be higher than what was reflected in this study. The reviews of medical record can
help researcher verifies the information. However, because of time constraint and
limited human resources, such review would not have been possible.

52

RECOMMENDATIONS
As demonstrated clearly in this study, the proportion of LDL-C target achievers and
nonachievers among patients with Type 2 Diabetes Mellitus and dyslipidaemia is still low in
our population and there was an association between HbA1c and LDL-C achievement.
Therefore, a holistic and intergrated approach should be intensified in targeting our patients
and health care providers especially in the management of patients with comorbid diabetes
and dyslipidaemia. All patients diagnosed with dyslipidaemia and diabetes should be given a
proper health education and awareness on the importance of achieving the target of the
diseases. These information should not only be informed during the diagnosing period but
must be continuous and persistent in every visit.
Training the health care providers in terms of good practice in the management of
dyslipidaemia and raising the awareness of our current treatment and guidelines would
improve our care towards these patients. All of these approaches had been carried out in our
setting but they still lack supervision and audit especially in the outpatient clinic in tertiary
centre. We need to design a better system in order to make sure that our patients get better
care. A dedicated education team in the clinic is very beneficial but the lack of human
resources rendered the approach non persistent and not optimized.
Since the adherence rate of statin therapy was very good through the use of this
instrument, we recommended the use of other tools or instruments in assessing adherence to
statin therapy to avoid overestimation of the result. The need to revalidate the tool used even
in a group within almost similar characteristic should be considered.
In future study, all the limitations that had been listed should be taken into consideration
for a better study result. Other important factors such as diet and physical activity should be
included future study.
53

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62.

Hammed IK, Abed BA, Rashid NF. Glycated haemoglobin as a dual biomarker

Association between HbA1c and dyslipidemia in type 2 diabetic patients.

63.

Khan CR, Weir GC, King gL, Jacobson AM. Joslin's Diabetes Mellitus 14 ed:

Lippincott Williams and Wilkins; 2005.

64.

Peters AL. Clinical relevance of non-HDL cholesterol in patients with diabetes.

Clinical diabetes. 2008;26(1):3-7.

65.

Suryawanshi N, Bhutey A, Nagdeote A, Jadhav A, Manoorkar G. Study of lipid

peroxide and lipid profile in diabetes mellitus. Indian Journal of Clinical Biochemistry.
2006;21(1):126-30.
66.

Schectman G, Hiatt J. Drug therapy for hypercholesterolemia in patients with

cardiovascular disease: Factors limiting achievement of lipid goals. The American Journal of
Medicine. 1996;100(2):197-204.
67.

Andrews TC, Ballantyne CM, Hsia JA, Kramer JH. Achieving and maintaining

national cholesterol education program low-density lipoprotein cholesterol goals with five
statins. The American Journal of Medicine. 2001;111(3):185-91.

59

APPENDIXES

60

Appendix 1

61

Appendix II

62

Appendix III
MAKLUMAT KAJIAN
Tajuk Kajian: Pencapaian Tahap Kolesterol Lipoprotein Berketumpatan Rendah, Faktor-faktor yang
mempengaruhinya dan Ketidakpatuhan Terhadap Ubat Antikolesterol Jenis Statin Dalam Kalangan
Pesakit Kencing Manis Jenis 2.
Nama Penyelidik:

Profesor Madya Dr. Shaiful Bahari Ismail (NO. MMC: 30837)

Dr. Nani Draman (NO. MMC: 35488 )
Dr. Norul Badriah Hassan
Dr Zainab Mat Yudin@Badrin (NO. MMC: 40301)

Pengenalan
Anda dipelawa untuk menyertai satu kajian penyelidikan secara sukarela. Sebelum menyertai kajian
ini, anda dikehendaki membaca dan memahami borang ini. Borang ini menerangkan tujuan kajian,
prosedur, risiko dan manfaat kajian. Ia juga menerangkan bahawa anda boleh menarik diri daripada
kajian ini pada bila-bila masa. Jika anda bersetuju menyertai kajian ini anda akan menerima salinan
borang ini untuk simpanan anda.
Sehubungan itu, anda diminta agar membaca dan memahami segala keterangan di bawah yang akan
memberi penerangan lanjut mengenai kajian ini.

Tujuan Kajian
Kajian ini dijalankan untuk mengukur tahap lipoprotein berketumpatan rendah yang dicapai
dan mengukur tahap kepatuhan pesakit terhadap ubat anti kolesterol jenis statin dalam
kalangan pesakit Kencing Manis Jenis 2. Daripada kajian ini juga, faktor-faktor yang
mempengaruhi lipoprotein berketumpatan rendah pesakit dapat dikaji. Ubat kolesterol jenis
statin telah terbukti keberkesanannya untuk menurunkan tahap kolesterol dalam darah yang
digunakan bukan sahaja untuk rawatan masalah kolesterol tinggi dalam darah tetapi juga
untuk pencegahan dan rawatan penyakit kardiovaskular. Kepatuhan pesakit terhadap
penggunaan ubat anti kolesterol jenis statin amat penting untuk memastikan keberkesannya.

Kelayakan Penyertaan
Doktor yang bertanggungjawab dalam kajian ini atau salah seorang kakitangan kajian telah
membincangkan kelayakan untuk menyertai kajian ini dengan anda. Adalah penting anda berterus

63

terang dengan doktor dan kakitangan tersebut tentang sejarah kesihatan anda. Anda tidak seharusnya
menyertai kajian ini sekiranya anda tidak memenuhi semua syarat kelayakan.

Beberapa keperluan untuk menyertai kajian ini adalah:

Kelayakan Penyertaan:
1. Berumur 18 tahun dan ke atas.
2. Pesakit telah disahkan menghidap penyakit Kencing Manis Jenis 2.
3. Pesakit telah disahkan menghidap penyakit Dyslipidaemia.
4. Dalam rawatan ubat anti kolesterol jenis statin sahaja selama 6 bulan atau lebih.

Anda tidak boleh menyertai kajian ini sekiranya:

1.

Anda mempunyai penyakit mental atau kerencatan otak.

2.

Anda tidak tahu membaca dan menulis.

3.

Tahap triglyceride > 4.3mmol/l

Prosedur-prosedur Kajian
Selepas anda memberi persetujuan bertulis untuk menjalani kajian ini anda akan diminta untuk
mengisi borang soal-selidik mengenai data peribadi serta menjawab soalan mengenai tahap kepatuhan
terhadap ubat antikolesterol jenis statin.
Jika anda mempunyai sebarang kemusykilan atau tidak memahami mana-mana bahagian di dalam
soal-selidik tersebut, anda bolehlah merujuk masalah tersebut kepada penyelidik yang akan sentiasa
berada di situ bagi membantu anda.

Risiko
Tiada sebarang risiko yang akan ditanggung oleh anda jika anda menyertai kajian ini.

Faedah
Hasil kajian ini adalah penting dalam meningkatkan kesedaran di kalangan pesakit kencing manis dan
hyperlipidaemia tentang kepentingan kepatuhan terhadap ubat antikolesterol.

64

Penyertaan Dalam Kajian

Penyertaan anda dalam kajian ini adalah secara sukarela. Anda boleh menolak untuk menyertai kajian
ini atau anda boleh menamatkan penyertaan anda pada bila-bila masa, tanpa sebarang hukuman atau
kehilangan manfaat yang sepatutnya anda perolehi.

Soalan
Sekiranya anda mempunyai sebarang soalan mengenai kajian ini atau hak-hak anda, sila hubungi
Dr Zainab Mat Yudin@Badrin,
Jabatan Perubatan Keluarga ,
Kampus Perubatan USM,
16150 Kubang Kerian Kelantan ( no tel : 0176822974)
Sekiranya anda mempunyai sebarang soalan berkaitan kelulusan Etika kajian ini, sila hubungi;
Puan Mazlita Zainal Abidin
Setiausaha Jawatankuasa Etika Penyelidikan (Manusia) USM
Pelantar Penyelidikan Sains Klinikal, USM Kampus Kesihatan.
No. Tel: 09-7663760 / 09-7663756
Kerahsiaan

Kajian ini adalah melibatkan isu-isu yang sensitif, semestinya identiti anda sebagai peserta
kajian adalah dirahsiakan. Segala maklumat yang bakal diperolehi dalam soal-selidik ini akan
sentiasa dirahsiakan dan hanya digunakan untuk tujuan kajian semata-mata. Ia juga tidak akan
didedahkan kepada umum melainkan atas perintah undang-undang.

Rekod anda yang asal mungkin akan dilihat oleh pihak universiti (Jabatan yang berkenaan), Lembaga
Etika kajian ini dan pihak berkuasa regulatori untuk tujuan mengesahkan prosedur dan/atau data
kajian klinikal. Maklumat anda mungkin akan disimpan dalam komputer dan diproses dengannya.

Dengan menandatangani borang persetujuan ini, anda membenarkan penelitian rekod, penyimpanan
maklumat dan pemindahan data seperti yang dihuraikan di atas.
Tandatangan
Untuk dimasukkan ke dalam kajian ini, anda mesti menandatangani serta mencatatkan tarikh halaman
tandatangan (Lihat contoh Borang Keizinan Peserta di LAMPIRAN 1 atau LAMPIRAN 2).

65

Borang Keizinan Peserta

Tajuk Kajian: Pencapaian Tahap Kolesterol Lipoprotein Berketumpatan Rendah, Faktor-faktor yang
mempengaruhinya dan Ketidakpatuhan Terhadap Ubat Antikolesterol Jenis Statin Dalam Kalangan
Pesakit Kencing Manis Jenis 2.
Nama Penyelidik:

Profesor Madya Dr. Shaiful Bahari Ismail (NO. MMC: 30837)

Dr. Nani Draman (NO. MMC: 35488 )
Dr. Norul Badriah Hassan
Dr Zainab Mat Yudin@Badrin (NO. MMC: 40301)

Untuk menyertai kajian ini, anda mesti menandatangani mukasurat ini.

Dengan menandatangani mukasurat ini, saya mengesahkan yang berikut:

Saya telah membaca semua maklumat dalam Borang Maklumat dan Keizinan
Peserta ini termasuk apa-apa maklumat berkaitan risiko yang ada dalam kajian
dan saya telah pun diberi masa yang mencukupi untuk mempertimbangkan
maklumat tersebut.
Semua soalan-soalan saya telah dijawab dengan memuaskan.
Saya, secara sukarela, bersetuju menyertai kajian penyelidikan ini, mematuhi
segala prosedur kajian dan memberi maklumat yang diperlukan kepada penyelidik
dan membenarkan rekod perubatan saya dianalisa bagi mendapatkan maklumat
yang berkaitan.
Saya boleh menamatkan penyertaan saya dalam kajian ini pada bila-bila masa.
Saya telah pun menerima satu salinan Borang Maklumat dan Keizinan Peserta
untuk simpanan peribadi saya.

Nama Peserta (Dicetak atau Ditaip)

No rujukan (disi oleh penyelidik)

No. Kad Pengenalan Peserta (Baru)

No. K/P (Lama)

Tandatangan Peserta

Tarikh (dd/MM/yy)

Nama & Tandatangan Individu yang Mengendalikan

Perbincangan Keizinan (Dicetak atau Ditaip)

Tarikh (dd/MM/yy)

Nama Saksi dan Tandatangan

Tarikh (dd/MM/yy)

66

LAMPIRAN 2
Borang Keizinan bagi Penerbitan Bahan yang berkaitan dengan Peserta
(Halaman Tandatangan)

Tajuk Kajian: Pencapaian Tahap Kolesterol Lipoprotein Berketumpatan Rendah, Faktor-faktor yang
mempengaruhinya dan Ketidakpatuhan Terhadap Ubat Antikolesterol Jenis Statin Dalam Kalangan
Pesakit Kencing Manis Jenis 2.
Nama Penyelidik:

Profesor Madya Dr. Shaiful Bahari Ismail (NO. MMC: 30837)

Dr. Nani Draman (NO. MMC: 35488 )
Dr. Norul Badriah Hassan
Dr Zainab Mat Yudin@Badrin (NO. MMC: 40301)
Untuk menyertai kajian ini, anda atau wakil sah anda mesti menandatangani mukasurat ini.
Dengan menandatangani mukasurat ini, saya memahami yang berikut:
Bahan yang akan diterbitkan tanpa dilampirkan dengan nama saya. Saya memahami,
walaubagaimanapun, ketanpanamaan yang sempurna tidak dapat dijamin.
Bahan
yang
akan
diterbitkan
dalam
penerbitan
mingguan/bulanan/dwibulanan/suku tahunan/dwi tahunan merupakan satu
penyebaran yang luas dan tersebar ke seluruh dunia. Kebanyakan penerbitan ini
akan tersebar kepada doktor-doktor dan juga bukan doktor termasuk ahli sains
dan ahli jurnal.
Bahan tersebut juga akan dilampirkan pada laman web jurnal di seluruh dunia.
Sesetengah laman web ini bebas dikunjungi oleh semua orang.
Bahan tersebut juga akan digunakan sebagai penerbitan tempatan dan
disampaikan oleh ramai doktor dan ahli sains di seluruh dunia.
Bahan tersebut juga akan digunakan sebagai penerbitan buku oleh penerbit jurnal.
Bahan tersebut tidak akan digunakan untuk pengiklanan ataupun bahan untuk
membungkus.
Saya juga memberi keizinan bahawa bahan tersebut boleh digunakan sebagai penerbitan lain
yang diminta oleh penerbit dengan kriteria berikut:
Bahan tersebut tidak akan digunakan untuk pengiklanan atau bahan untuk
membungkus.
Bahan tersebut tidak akan digunakan di luar konteks contohnya: Gambar tidak
akan digunakan untuk menggambarkan sesuatu artikel yang tidak berkaitan
dengan subjek dalam foto tersebut.
Nama Peserta (Dicetak atau Ditaip)
No. Kad Pengenalan Peserta

No rujukan (disi oleh penyelidik)

T/tangan Peserta

Nama & Tandatangan Individu yang Mengendalikan

Tarikh (dd/MM/yy)
Tarikh (dd/MM/yy)

Perbincangan Keizinan (Dicetak atau Ditaip)

Nota:

i)

Lebihan sampel kajian ini akan dilupuskan dan tidak akan digunakan untuk

tujuan lain kecuali setelah mendapat kebenaran daripada Jawatankuasa Etika Penyelidikan
(Manusia), USM.

67

Appendix IV

CASE REPORT FORM

Low density lipoprotein cholesterol target achievement, associated factors with

nonachievement to LDL-C target and adherence to statin therapy among patients with
Type 2 Diabetes Mellitus

68

NO SIRI:

KOD PESAKI:

A) SOCIO DEMOGRAPHY

1.

Address : .............................................................
.............................................................

2.

Sex :

Male

Female

3.

Age :

4.

Ethnic group :

Malay

Chinese

Indian

5.

Marital status :

Married

Single

Widow/widower

6.

Smoking :

Smoker

Ex-smoker

Non-smoker

Years

How many cigarettes do you smoke per day?

7.

Others:................

1-5

6-10

11-20

more than 20

Occupation : _____________________

8. Total Household Monthly Income (Ringgit Malaysia):

9.

Less than RM440

RM440 - RM700

RM701 - RM1999

more than RM2000

Highest Academic Qualification:

None

Standard Six

Sijil Rendah Pelajaran(SRP)/

Penilaian Menengah Rendah(PMR)

Sijil Pelajaran Malaysia(SPM)

Sijil Tinggi Pelajaran Malaysia(STPM)

Diploma

Others: _________________

Ijazah

69

B) PATIENTS TREATMENT
1. List of medications taken:
Bil

Name of drugs

Dose

Frequency of medication taken per

day

C) EXAMINATION AND INVESTIGATIONS

INVESTIGATION
1) Weight
2) Height
3) BMI
4) Blood Pressure
5) HbA1c
6) Lipid profile

RESULT

70

TC: ____ mmol/l

kg
m
Kg/m2
mmHg
%
LDL: ____mmol/l

TG: ____mmol/l

HDL:____mmol/l

TARIKH :
Hari

Bulan

Tahun

SOAL SELIDIK KAJIAN KEPATUHAN PESAKIT TERHADAP UBAT KOLESTEROL

Sila tandakan pada kotak yang berkenaan berdasarkan lawatan akhir anda ke klinik ini.

(1) MAKLUMAT RAWATAN PESAKIT

Sila tandakan pada kotak yang berkenaan berdasarkan lawatan akhir anda ke klinik ini.

1) Sudah berapa lama anda makan ubat kolesterol :

6 bulan hingga 1 tahun

Lebih daripada 1 tahun hingga 5 tahun

Lebih daripada 5 tahun

Tidak tahu/ tidak pasti

2) Adakah anda tahu nama ubat kolesterol yang anda makan?

Ya

Tidak

Jika jawapan anda ialah Ya, apakah nama ubat antikolesterol tersebut?
Lovastatin/Mevacor/Altocor

Simvastatin/Zocor

Atovastatin/Lipitor/Torvast

Rosuvastatin/Crestor

Pravastatin/Pravachol/Selektine/Lipostat
Amlodipine+atorvastatin/Caduet

3)Berapakah dos ubat kolesterol anda makan?

10 mg

20 mg

40 mg

60 mg

80mg

Tidak tahu

71

4) Adakah anda pernah mengalami gejala-gejala kesan sampingan ubat kolesterol seperti
berikut:
Sembelit/ sakit ulu hati/ sekak perut/ sakit perut/ loya/ muntah
Sakit otot/badan
Pening kepala/ sakit kepala
Kegatalan kulit
Lain-lain; nyatakan:_______________________

72

(2) SOALSELIDIKAMALANPENGAMBILANUBATKOLESTEROL

Silabulatkan()jawapanyangpalingsesuaibagianda(dalammasaduabulanyanglepas)mengikut
skalaberikut:
Tidak
Pernah

Jarang

Kadang

Kerap

Kadang

Sangat
Kerap

1)

Andamengambil/memakanubatsepertiyang
diarahkanolehdoktor

2)

Andamengambil/memakanubathanyaapabila
andamerasakurangsihat

3)

Anda merasa sukar/ susah untuk mengambil/

memakanubatsetiaphari

4)

Andaterlupamengambil/memakanubat

5)

Bilaandaterlupamengambil/ memakanubat,
anda makan ubat yang seterusnya dua kali
gandadariyangdiarahkanolehdoktor

6)

Andaubah masamengambil/memakanubat
tanpanasihatdoktor

7)

Andakurangkanpengambilan/ memakanubat
apabilamerasasihatatausegar

8)

Anda berhenti mengambil/ memakan ubat

apabilamerasaubatitutidakberkesan

9)

Anda berhenti mengambil/ memakan ubat

apabilamengalamikesanyangtidakenakdari
ubatyangdimakantanpanasihatdoktor

10)

Anda berhenti mengambil/ memakan ubat

apabilamerasasihatatausegar

73