Association between vitamin D status and coronary heart disease among adults in Saudi Arabia

283 Pages·2017·2.24 MB·English

Association between vitamin D status and coronary heart disease
among adults in Saudi Arabia: a case-control study
Najlaa Aljefree
Bachelor of Food and Nutrition (King Abdull-Aziz University, Jeddah, Saudi Arabia)
Master of Food and Nutrition (King Abdull-Aziz University, Jeddah, Saudi Arabia)
Master of Business (University of Newcastle, Newcastle, Australia)
A thesis submitted in fulfilment of the requirements of the degree of
Doctor of Philosophy
School of Medicine
Public Health
Griffith University
Menzies Health Institute Queensland
July 2017
1
Summary
Accumulating evidence suggests that vitamin D deficiency and insufficiency may
play a role in the development of coronary heart disease (CHD) and associated risk factors.
Saudi Arabia has witnessed a growing epidemic of CHD and associated risk factors during
the last few decades for several reasons, including the rapid changes in lifestyle and
urbanization. Furthermore, national studies have demonstrated that vitamin D deficiency is
highly prevalent in Saudi Arabia. Thus, it is crucial to examine the function of vitamin D in
the prevention of CHD in Saudi Arabia. Therefore, the aim of this study was to examine the
association between vitamin D status and the risk of CHD among adults in Saudi Arabia. It
also examined the association between vitamin D deficiency and cardio-metabolic risk
factors, including obesity, diabetes, hypertension and hypercholesterolemia, among subjects
with and without CHD in Saudi Arabia. In addition, the present study attempted to compare
the levels of knowledge, attitudes and behaviours related to vitamin D between subjects with
and without CHD. It also examined the association of vitamin D status with knowledge,
attitudes and behaviours related to vitamin D among study subjects. A qualitative approach
was used in this study to further understand of study subjects’ knowledge about vitamin D
and attitudes toward sun exposure. It also explored the social and cultural factors which may
explain for the high prevalence of vitamin D deficiency in Saudi Arabia.
This mixed methods research involved both quantitative and qualitative approaches.
For the quantitative research, a case-control study was conducted between May and October
2015. The study participants included 130 CHD cases and 195 controls who were recruited
from three hospitals in the western region of Saudi Arabia. The King Abdullah Medical City
(KAMC) and Tunsi private hospital were located in Makkah city, and King Abdul Aziz
University Hospital (KAU) was located in Jeddah city. Face-to-face interviews were
ii
conducted to collect data on participants’ socio-demographic characteristics, family history of
CHD, knowledge about vitamin D, attitudes toward sun exposure and vitamin D-related
behaviours, including sun exposure behaviours, use of sun protection, intake of vitamin
supplementation and consumption of foods rich in vitamin D. Furthermore, blood pressure
measurements and anthropometric measurements were also taken. In addition, fasting blood
samples were collected from study participants to measure serum levels of vitamin D, blood
glucose and total cholesterol. This research project has also conducted qualitative in-depth
interviews with 22 subjects who participated in the quantitative study. The qualitative study
was conducted at the same hospitals and during the same data collection period. The
interviews consisted of open-ended questions adapted from the existing literature.
The results of the case-control study demonstrated that vitamin D deficiency (serum
25(OH)D < 10 ng/mL) was significantly higher in CHD cases than in the controls (46% and
3%, respectively) (p < 0.001). It also showed that a relatively higher proportion of CHD cases
had obesity (44% and 22%, respectively) and diabetes (35% and 14%, respectively) (p <
0.001) than controls. However, controls had significantly higher total serum cholesterol levels
than CHD cases (13% and 5%, respectively) (p < 0.001). Moreover, the results indicated that
vitamin D deficiency (serum 25(OH)D < 20 ng/mL) was significantly associated with
increased risk of CHD (OR: 6.5, 95% CI: 2.7–15, p < 0.001) among adults in Saudi Arabia.
When the associations between vitamin D status and cardio-metabolic risk factors were
examined in subjects with and without CHD separately, the results showed that in subjects
with CHD, vitamin D deficiency (serum 25(OH)D < 20 ng/mL) was significantly associated
with an increased risk of diabetes (OR: 2.9, 95% CI: 1.02-8.5, p=0.04). However, no
significant association was found between vitamin D deficiency and other cardio-metabolic
risk factors (obesity, hypertension and hypercholesterolemia) in subjects with CHD. In
contrast, in subjects without CHD, no significant associations were found between vitamin D
iii
deficiency (serum 25(OH)D < 20 ng/mL) and cardio-metabolic risk factors (diabetes, obesity,
hypertension and hypercholesterolemia).
In relation to the comparison between subjects with and without CHD in terms of
knowledge, attitudes and behaviours related to vitamin D, the results indicated that total
knowledge score was higher in the control subjects than in the CHD subjects [2.5 (±1.8) and
1.6 (±2.2), respectively]. The CHD cases had better attitudes toward sun exposure than the
control subjects, but the controls had better attitudes toward vitamin D than CHD cases
(p = 0.001). In addition, the control subjects had a higher intake of multivitamin supplements
compared to CHD cases (6.7% and 0.8%, respectively; p = 0.010). Similarly, the control
subjects had a higher intake of butter (p = 0.001), oily fish (p = 0.004) and liver (p = 0.003)
compared to the CHD cases; however, the CHD cases had a significantly higher intake of
milk (p = 0.001). The results also demonstrated that vitamin D deficiency (serum 25(OH)D <
20 ng/mL) was significantly associated with low levels of knowledge about vitamin D (95%
CI: 1.08–3.06, P = 0.024) as well as low intake of vitamin supplements including vitamin D,
calcium, multivitamin and calcium supplements with vitamin D (95% CI: 2.12–
8.92, P < 0.001).
The results of the qualitative study showed that the participants had reasonable levels
of knowledge about vitamin D in some aspects, including the impact of vitamin D deficiency
on bone health and exposure to sunlight as the key source of vitamin D. The participants also
understood that the intake of vitamin D supplements is important to improve vitamin D
status. There was a lack of adequate knowledge on food sources of vitamin D and the health
effects of vitamin D deficiency, except for bone health. Although some participants had
positive attitudes towards exposure to sunlight, it was restricted to the time of day, as they
avoided hot temperatures during the middle of the day. Also, they only exposed their faces
and hands to sunlight. In comparison, some participants had negative attitudes about exposure
iv
to sunlight and avoided sunlight. Also, participants identified a number of barriers that
prevented them from receiving sufficient sunlight. These barriers included hot weather,
changes in house designs and living in high-rise buildings, shortage of public areas, physical
inactivity, and some religious principles such as wearing hijab. Finally, the study results
identified some gender differences regarding adopting healthy behaviours to increase vitamin
D status as female participants were more enthusiastic about carrying out behaviours that
would improve their vitamin D status than male participants.
In conclusion, this research indicated an inverse association between vitamin D
deficiency and increased risk of CHD among adults in Saudi Arabia. It also added some
valuable insights on the knowledge, attitudes and behaviours related to vitamin D among
adults in the country. These results emphasize the importance of addressing vitamin D
deficiency in Saudi Arabia as a potential modifiable factor to reduce the incidence of CHD
and associated risk factors in future generations. The results of this research may have
important implications for the development of strategies to improve vitamin D status in the
population living in Saudi Arabia and thereby help prevent the development of CHD.
Key words: vitamin D deficiency, coronary heart disease, diabetes, obesity, knowledge,
attitudes, sun exposure, vitamin D supplements, Saudi Arabia, Middle East.

v
Statement of Originality
This thesis describes original research conducted by Najlaa Aljefree in the School of
Medicine at Griffith University. This work has not previously been submitted for a degree in
any university. To the best of my knowledge and belief, the thesis contains no material
previously published or written by another person except where due reference is made in the
thesis itself.
Najlaa Aljefree
vi
Acknowledgements
This dissertation would not have been successfully completed without the
collaboration and support of a number of people. I would like to first thank my principal
supervisor, Associate Professor Faruk Ahmed, for his guidance, trust, honesty, support and
encouragement. I would also like to thank my second supervisor, Dr Patricia Lee, for her
patience, encouragement and hard work. Thanks to both of you for having faith in me. Your
combination of enthusiasm with a scientific mind and long academic experience helped me
overcome obstacles during my PhD program. Your doors were always open to me, and you
always provided immediate response to my questions and concerns, so thank you for that.
To my parents and sisters, who provided love throughout my journey, thank you for
your extraordinary love, support and sacrifice and for encouraging me to achieve what I have
achieved.
To my friends, Rimante Ronto, Elham Nikbakht Nasrabadi, and Nasim Salehi, thank
you for your smiles, small talk and laughs. These years would not have been the same
without you.
Finally, to my husband and best friend, Hussein Alattas, thank you for everything and
for being patient and supportive throughout my ups and downs.
vii
Table of Content
Summary .................................................................................................................................... ii
Statement of Originality ............................................................................................................ vi
Acknowledgements .................................................................................................................. vii
Table of Content .................................................................................................................... viii
List of Tables ......................................................................................................................... xiii
List of Figures ......................................................................................................................... xiv
List of Acronyms and Symbols ............................................................................................... xv
Publications, Presentations and Awards: ............................................................................... xvii
Chapter 1: Introduction ............................................................................................................ 20
1.1 Background and rationale of the study:.......................................................................... 20
1.2 Research objectives: .................................................................................................. 24
1.3 Research questions: ........................................................................................................ 25
1.4 Significance of the research: .......................................................................................... 26
1.5 Thesis structure and outline of chapters: ........................................................................ 27
Chapter 2: Literature review .................................................................................................... 31
2.1 Introduction .................................................................................................................... 31
2.2 Cardiovascular disease ................................................................................................... 31
2.2.1 Definitions and types: .............................................................................................. 31
2.2.2 The burden of CVD and associated risk factors: ..................................................... 32
2.3 Saudi Arabia ................................................................................................................... 33
2.4 Prevalence of cardiovascular disease and associated risk factors among adult
population in the gulf region: a systematic review (Manuscript 1)...................................... 35
2.4.1 Introduction ............................................................................................................. 35
2.4.2 Abstract .................................................................................................................... 37
2.4.3 Introduction ............................................................................................................. 38
2.4.4 Methods ................................................................................................................... 39
2.4.5 Results ..................................................................................................................... 43
2.4.6 Discussion:............................................................................................................... 64
2.4.7 Conclusion: .............................................................................................................. 68
2.4.8 References: .............................................................................................................. 68
2.5 Vitamin D: Background ................................................................................................. 76
viii
2.5.1 The definition and metabolism of vitamin D: ......................................................... 76
2.5.2 Vitamin D deficiency: ............................................................................................. 77
2.5.3 Recommendation for vitamin D intake: .................................................................. 78
2.5.4 Risk factors for vitamin D deficiency: .................................................................... 79
2.5.5 The global epidemiology of vitamin D deficiency: ................................................. 80
2.5.6 The prevalence of vitamin D deficiency in Saudi Arabia: ...................................... 81
2.5.7 Knowledge and attitudes in relation to vitamin D: .................................................. 83
2.6 Vitamin D and Coronary heart disease .......................................................................... 85
2.6.1 The mechanism by which vitamin D defends against CHD: ................................... 85
2.6.2 Studies on vitamin D and risk of CHD: ................................................................... 87
2.7 Conclusion:..................................................................................................................... 95
Chapter 3: Research Methodology........................................................................................... 97
3.1 Introduction: ................................................................................................................... 97
3.2 Research paradigm: ........................................................................................................ 97
3.3 Study design: .................................................................................................................. 98
3.4 Conceptual framework: .................................................................................................. 99
3.5 Study population: ......................................................................................................... 103
3.5.1 Research setting: .................................................................................................... 103
3.5.2 Cases’ definition and selection: ............................................................................. 103
3.5.3 Controls’ definition and selection: ........................................................................ 104
3.5.4 Inclusion and exclusion criteria for study subjects: ............................................... 104
3.6 Sample size:.................................................................................................................. 105
3.7 Data collection methods: .............................................................................................. 105
3.7.1 Quantitative data: ................................................................................................... 105
3.7.2 Qualitative data: ..................................................................................................... 107
3.8 Variables and measurements: ....................................................................................... 108
3.9 Project management and research procedure: .............................................................. 112
3.10 Ethical considerations: ............................................................................................... 114
3.11 Data analysis: ............................................................................................................. 114
3.11.1 Quantitative data analysis: ................................................................................... 114
3.11.2 Qualitative data analysis: ..................................................................................... 117
3.12 Rigour (validity and reliability of the study):............................................................. 117
3.13 Conclusion:................................................................................................................. 118
ix
Chapter 4: Association between Vitamin D Status and Coronary Heart Disease among Adults
in Saudi Arabia: A Case-Control Study (Manuscript 2) ........................................................ 119
4.1 Introduction ............................................................................................................. 119
4.2 Abstract: ....................................................................................................................... 121
4.3 Introduction: ................................................................................................................. 121
4.4 Materials and Methods ................................................................................................. 123
4.4.1 Study Design and Population ................................................................................ 123
4.4.2 Inclusion and Exclusion Criteria ........................................................................... 126
4.4.3 Data Collection ...................................................................................................... 126
4.4.4 Biochemical Measurements ................................................................................... 127
4.4.5 Statistical Analysis ................................................................................................ 128
4.5 Results .......................................................................................................................... 129
4.6 Discussion .................................................................................................................... 133
4.7 Conclusions .................................................................................................................. 136
4.8 References .................................................................................................................... 136
Chapter 5: Association between Vitamin D Status and Cardio-Metabolic Risk Factors among
Adults with and without Coronary Heart Disease in Saudi Arabia (Manuscript 3) .............. 140
5.1 Introduction ............................................................................................................. 140
5.2 Abstract ........................................................................................................................ 142
5.3 Introduction: ................................................................................................................. 143
5.4 Methods: ....................................................................................................................... 145
5.5 Results .......................................................................................................................... 149
5.6 Discussion .................................................................................................................... 153
5.7 Conclusion .................................................................................................................... 156
Chapter 6: Knowledge and attitudes about vitamin D, and behaviors related to vitamin D in
adults with and without coronary heart disease in Saudi Arabia (Manuscript 4) .................. 161
6.1 Introduction .................................................................................................................. 161
6.2 Abstract ........................................................................................................................ 163
6.3 Introduction .................................................................................................................. 164
6.4 Methods ................................................................................................................... 166
6.4.1 Study population ....................................................................................................... 166
6.4.2 Data collection ....................................................................................................... 167
6.4.3 Biochemical measurements ................................................................................... 168
6.4.4 Statistical analysis.................................................................................................. 169
x