Dietary supplementation and engaging in physical activity as predictors of coronary artery disease...

CARDIAC CARE

Dietary supplementation and engaging in physical activity as

predictors of coronary artery disease among middle-aged women

Ching-Ching Tsai, Ming-Hsiung Hsieh, Ai-Hsien Li, Ping-Ling Chen and Chii Jeng

Aim and objectives. To explore risk factors for coronary artery disease (CAD) among middle-aged women in Taiwan.

Background. Coronary artery disease is a leading cause of death among females. Risk factors for CAD vary due to differ-

ences in ethnicity, gender and age. However, few studies have documented risk factors among middle-aged women.

Design. We employed a cross-sectional, comparative study design.

Methods. Sixty-five middle-aged women who were suspected of having CAD and who received cardiac catheterisation were

purposively sampled and divided into a CAD group (with at least one coronary artery with > 50% stenosis) and a control

group, according to the results of catheterisation. Individual questionnaires regarding their medical history, blood test results,

sociodemographic characteristics, metabolism, biomarkers and lifestyle risk factors were administered and quantified.

Results. The mean age of the 65 women (31 CAD and 34 controls) was 56�2 years. Within the CAD group, there was a

greater incidence of women with a history of diabetes mellitus (DM), increased fasting blood glucose and increased diastolic

blood pressure. Comparatively fewer women within the CAD category used dietary supplements or had a lower level of

physical activity. After adjusting for other confounders, it was discovered that women who used dietary supplements

(OR = 0�28; p = 0�04) and engaged in physical activities (OR = 0�16; p = 0�02) were less likely to develop CAD.

Conclusions. Use of dietary supplements and engaging in physical activities can significantly predict the incidence of CAD

among middle-aged women in Taiwan.

Relevance to clinical practice. Middle-aged women should be encouraged to take appropriate dietary supplements and

engage in physical activity in order to prevent CAD.

Key words: coronary artery disease, dietary supplement, middle age, physical activity, women

Accepted for publication: 4 January 2013

Introduction

The World Health Organization (WHO) estimates that

7�3 million people globally died of coronary artery disease

(CAD) in 2008 (WHO 2011). In Europe, 23% of female

mortality was due to CAD (Stramba-Badiale et al. 2006).

In the United States, the death rate from CAD among

females has exceeded that of males since 1984 and CAD

has become the leading cause of death among females

(Roger et al. 2011). In Taiwan, heart disease was the

Authors: Ching-Ching Tsai, PhD Candidate, Lecturer, Graduate

Institute of Nursing, College of Nursing, Taipei Medical University,

Taipei and Department of Nursing, Chang Gung University of

Science and Technology, Tao Yuan; Ming-Hsiung Hsieh, MD,

Director, Division of Cardiovascular Medicine, Department of

Internal Medicine, Wan Fang Hospital, Taipei Medical University,

Taipei and Associate Professor, Department of Internal Medicine,

School of Medicine, College of Medicine, Taipei Medical Univer-

sity, Taipei; Ai-Hsien Li, MD, PhD, Assistant Professor, Division

of Cardiology, Cardiovascular Center, Far-Eastern Memorial Hos-

pital, Taipei, Adjunct Assistant Professor, College of Medicine,

National Taiwan University Hospital, Taipei and Department of

Biomedical Engineering, Chung-Yuan Christian University,

Chung-Li; Ping-Ling Chen, PhD, MPH, Professor, Graduate Insti-

tute of Injury Prevention and Control, College of Public Health

and Nutrition, Taipei Medical University, Taipei; Chii Jeng, PhD,

Professor, Graduate Institute of Nursing, College of Nursing,

Taipei Medical University, Taipei, Taiwan

Correspondence: Chii Jeng, Professor, Graduate Institute of

Nursing, College of Nursing, Taipei Medical University, 250,

Wu-Shin Street, Taipei, Taiwan. Telephone: +886 2 23777438.

E-mail: [email protected]

© 2013 John Wiley & Sons Ltd

Journal of Clinical Nursing, 22, 2487–2498, doi: 10.1111/jocn.12263 2487

second leading cause of death in women in 2011. It

accounted for 11�2% of total deaths, which is higher than

the rate in males of 10�6%. In women aged 40–64 years,

heart disease was the sixth leading cause of death in 2005

and has become the second most common cause of death

since 2008 (Department of Health, Executive Yuan 2012a).

Therefore, this disease is a serious health problem among

middle-aged women in Taiwan.

Prevention of CAD relies principally on reducing tradi-

tional risk factors (RFs) and addressing emerging RFs.

The term ‘RF’ was first introduced in the Framingham

study in 1961 (Schnohr et al. 2002). The INTERHEART

study collected and analysed incidences of first episodes

of myocardial infarction between 1993–2003 in 52 coun-

tries. Results showed that nine traditional RFs – dyslip-

idaemia, hypertension (HTN), diabetes mellitus (DM),

obesity, smoking, alcohol consumption, diet, physical

activity and psychosocial factors – could predict up to

94% of the population-attributable risks for myocardial

infarction (Anand et al. 2008). In 2001, the Adult Treat-

ment Panel (ATP) III of the National Cholesterol Educa-

tion Program (NCEP) first proposed the term ‘emerging

RFs’ in recognition of the need to include homocysteine

(Hcy) and other proinflammatory factors in addition to

traditional RFs (Expert Panel on Detection 2001). Inclu-

sion of other RFs like high-sensitivity C-reactive protein

(hsCRP) (Rasouli & Kiasari 2006) and leptin (Reilly

et al. 2004) will improve the sensitivity and effectiveness

of detection. As proinflammatory factors are produced via

different pathways, simultaneous analysis of two or more

biomarkers will increase the detection sensitivity for

assessing CAD risk.

Risk factors for CAD differ based on gender; thus, an

understanding of RFs relevant to females can reduce pre-

vention costs and simultaneously improve intervention effi-

cacies. The Copenhagen City Heart Study, a generational

study that followed subjects for 21 years, found that the

top four RFs for CAD (DM, smoking, HTN and reduced

physical activity) in both males and females were the same,

but the degree of importance of each RF varied according

to age and gender (Schnohr et al. 2002). Anand et al.

(2008) used INTERHEART study data and compared the

differences in RFs between male and female subjects. They

found that females had a higher odds ratio (OR) of devel-

oping CAD due to HTN and DM compared to males, while

physical activity and moderate drinking conferred a greater

degree of protection. These differences might be associated

with oestrogen, nitric oxide (NO) production, energy

metabolism and effects of the Y chromosome (Blum &

Blum 2009).

In the Women’s Health Study (WHS), a female follow-up

study, an assessment of hsCRP and other RFs dramatically

increased the predictability of cardiovascular disease (CVD)

in 10 years (Cook et al. 2006). Ridker et al. (2007) analy-

sed 35 traditional RFs and emerging RFs in the WHS and

found that age, systolic blood pressure (SBP), glycated hae-

moglobin (HbA1c), smoking, total cholesterol (TC), high-

density lipoprotein (HDL), hsCRP and a family history of

premature CAD significantly predicted the risk of develop-

ing CVD in 10 years, which provided a better degree of fit

than predictive models used in the Framingham study

(Wilson et al. 1998) and ATP III study (Expert Panel on

Detection 2001). In 1999, the American Heart Association

(AHA) first proposed policy guidelines for preventing CVD

in females, and in 2011, it was reported that DM was an

independent risk factor for CAD. Only those with a healthy

lifestyle without RFs belonged to the ideal cardiovascular

health group. Such an ideal group was defined as those not

receiving treatment while having clinical parameters that

included TC < 200 mg, blood pressure (BP) < 120/

80 mmHg, FBG < 100 mg/dl, a body mass index (BMI) of

< 25 kg/m2, no smoking and either moderate physical

activity of � 150 minute/week, rigorous physical activity

� 75 minute/week or a combination of the two, while also

following a healthy Dietary Approach to Stop Hypertension

(DASH) diet (Mosca et al. 2011).

Neither current female CAD research studies nor clinical

guidelines take age into consideration. Physiologically, as

middle-aged women approach menopause, they enter a

transition period of ageing. Regardless of the occupational

status, these Taiwanese women have the responsibility and

associated pressures of looking after their family in this

transition period. Therefore, the health status of women

has individual and also broader societal impacts. Priorities

and goals in life vary with age, and as a consequence, life-

styles also change accordingly. An investigation of the RFs

for CAD in middle-aged women would allow for early pre-

vention and reductions in the incidence and severity of

CAD in older age. The aim of this study was to investigate

the RFs for CAD among middle-aged women in Taiwan in

order to apply them to the prevention, detection and treat-

ment of CAD.

Methods

Study population

This was a cross-sectional, comparative study. Patients were

selected from the cardiovascular department of two medical

centres in Taipei, Taiwan. Female patients who were


2488 Journal of Clinical Nursing, 22, 2487–2498

C-C Tsai et al.

suspected of having CAD and were admitted for catheteri-

sation were divided into CAD and control groups based on

their results. In the CAD group, at least one main coronary

artery among the left anterior descending, left circumflex

and right coronary artery had to have stenosis of > 50%.

The control group had no abnormalities in the coronary

arteries. Inclusion criteria for this study were as follows: (1)

being aged 40–64 years and (2) able to speak Mandarin or

Taiwanese. Exclusion criteria for this study included having

(1) a prior diagnosis of psychiatric conditions or end-stage

renal disease (ESRD); (2) a bilateral oophorectomy; or (3)

serious infection, trauma or surgery in the previous

2 weeks.

In total, 723 women received catheterisation from

February 2010–December 2011, including 140 women who

were middle aged. Eighteen of these women were excluded

due to ESRD (8), psychiatric problems (7), surgically

induced menopause (2) or impaired hearing (1). Among the

122 eligible subjects, 28 refused to participate because of

feeling troubled, lacking time, experiencing discomfort and

having no family support, and another three subjects were

excluded because of incomplete data. Therefore, only 91

subjects were recruited for this study. There were no differ-

ences between these 91 subjects who agreed to participate

and the 28 subjects who refused to participate in terms of

age, the number of stenotic coronary arteries or the number

of stents implanted (p > 0�05). Of the 91 subjects, 31 were

diagnosed with CAD, 34 had no stenosis, and the remain-

ing 26 had stenosis of � 50% and were excluded from the

data analysis.

Measurement of study variables

Risk factors in this study were categorised into sociodemo-

graphic characteristics, metabolism, biomarkers and life-

style. Details of the measurement methods and instruments

are given below.

Sociodemographic characteristics

Sociodemographic characteristics, including age, educa-

tional level, marital status, menopausal status, occupation

and medical history, were collected through questionnaires.

If the volume and interval of menses were similar to previ-

ous cycles, or irregular for a period of < 3 months, the sub-

jects were considered to be premenopausal. If irregular

menses had lasted for more than 3 months, or if menses

had ceased over a period of < 1 year, subjects were consid-

ered to be perimenopausal. If menses had ceased for more

than 12 continuous months, the subjects were considered

to be postmenopausal. Subjects were asked whether they

had chronic systemic diseases such as DM, HTN, dyslipida-

emia, cerebrovascular accidents, renal insufficiency and/or

gout. If participants answered ‘yes’, they were further ques-

tioned as to the course of the disease and whether they had

been taking medications regularly. Subjects were queried

about hormone replacement therapy in the past 12 months.

Subjects were also asked whether they had used any dietary

supplements in the past 12 months. If the answer was ‘yes’,

they were queried about the use of multivitamins, B-com-

plex factors, B2, B6, B12, folate, Fe, Ca, vitamins D, C, E

and others. A family history of premature CAD was con-

sidered if relatives, including grandparents, parents and/or

siblings, had suffered from CAD before the age of

60 years.

Metabolic factors

Metabolic factors that were considered included DM,

HTN, dyslipidaemia and obesity. Data about the FBG,

SBP, DBP, triglycerides (TGs), HDL, low-density lipopro-

tein (LDL), TC, body height (BH) and body weight (BW)

were collected by checking clinical records at the time of

admission. If these data were not available, then data col-

lected in the outpatient setting within a half year before the

admission were used. The HDL/LDL ratio and BMI were

calculated. The waist circumference (WC) and hip circum-

ference (HC) were measured with a measuring tape (to the

nearest 0�1 cm). The WC was measured at the middle point

between the anterior superior iliac spine (ASIS) and the

lower edge of the rib at end expiration when a subject was

standing (and wearing a thin layer of clothes). The HC was

measured at the largest circumference of the hip. The

waist-to-hip ratio (WHR) was calculated as WC/HC (Corn-

ier et al. 2011).

Biomarker factors

Biomarkers that were assessed from serum included hsCRP,

Hcy and leptin. Six millilitres of blood was taken from the

catheter after fasting for 6 hour, and 3 ml was aliquoted

into two blood-collecting tubes (one with EDTA and the

other with only gel). The blood was then centrifuged,

stored on ice in the hospital laboratory and transported to

the corresponding certified pathology diagnostic centre for

testing within 24 hour. HsCRP was measured by immuno-

turbidimetry (Siemens Advia 1800, Tarrytown, NY, USA)

with a coefficient of variation (CV) of 0�6–1�4%. Hcy was

measured by chemiluminescence (CLIA; Siemens Advia

Centaur, Tarrytown, NY, USA) with a CV of 4�5–8�2%.

Leptin was measured using an enzyme-linked immunosor-

bent assay (ELISA; Bio-Rad, Kansas City, MO, USA) with

a CV of 0�1–2�3%.


Journal of Clinical Nursing, 22, 2487–2498 2489

Cardiac care Dietary supplementation and physical activity engagement as predictors

Lifestyle factors

Data on lifestyle factors, including smoking, exposure to

second-hand smoke (SHS), alcohol intake, diet, physical

activity, depression and anxiety, were collected through

questionnaires. If the subjects had smoked fewer than 100

cigarettes by the time of questioning, they were classified

as non-smokers. If they had smoked > 100 cigarettes and

had stopped smoking for > 1 year, they were classified as

past smokers. If someone at home or in the public had

smoked in the presence of a subject during the past week,

that subject was classified as having had SHS exposure.

Subjects were asked whether they had consumed alcohol

in the past 2 weeks. If the answer was ‘yes’, then they

were asked about the type (according to the ratio index

of alcohol by the Taiwan Tobacco & Liquor Corpora-

tion) and amount (a cup being equal to 150 ml) of

alcohol, in addition to the frequency of drinking every

week. The average drinking amount was calculated by

the formula: (ratio index 9 amount (ml) 9 frequency)/7.

The recommended amount of alcohol intake for women,

according to the AHA, is < 12 g/day. Subjects were then

categorised using the cut-off value of 12 g/day (Mosca

et al. 2011).

The computer-assisted Chinese Food Frequency Ques-

tionnaire (FFQ) is an efficient questionnaire developed by

Academia Sinica, Taiwan (N.H. Yei, National Taiwan Uni-

versity, Taipei, unpublished Master’s Thesis). This tool is

used to assess the dietary situation in the past month by

asking about the type of food consumed and the frequency

of having this food. This questionnaire includes dietary

items with an intake frequency response of > 87% in the

1993–1996 Nutrition and Health Survey in Taiwan study.

Such items were then classified into 14 major categories

under which three to nine subcategories were listed. This

provided a table of diverse food. The frequency was based

on daily, weekly or monthly intake. Food intake was

assessed using frequently used units (one bowl of food),

typical amounts (one egg) or atypical amounts (which

required self-made tools and pictures for assessment). The

food characteristics also assessed the use of cooking oil,

cooking methods, skinned meat and egg yolk. Nutrients of

the food were analysed based on a database of food ingre-

dients in Taiwan, ingredients of common foods produced in

Taiwan, tables of food ingredients and nutrient databases

from the US Department of Agriculture (USDA). These data

were then sent to the National Health Research Institute

for analysis, and the daily intake of each food ingredient

was calculated. A residual analysis, conducted with SAS 9.0

software (SAS institute, Cary, North California, USA), was

applied to energy calibration in order to acquire the

adjusted cholesterol and saturated fatty acid (SFA) intake.

The percentage of the adjusted SFA over total energy intake

was calculated with the formula: (adjusted SFA

intake 9 9 � 1000) � total energy intake 9 100. By com-

paring data with the AHA recommended intake of choles-

terol (< 150 mg/day) and SFA percentage (< 7% of total

energy intake), an inadequate diet was defined as choles-

terol intake of � 150 mg and an SFA/total energy intake

of � 7% (Mosca et al. 2011).

Physical activity was assessed by asking whether the sub-

jects had exercised in the past 2 weeks apart from their

work, daily life and chores. If the answer was ‘no’, partici-

pants were considered to be inactive; if the answer was

‘yes’, then participants were asked further about the type of

activity engaged in (including walking, running, climbing,

swimming, cycling, playing ball, gymnastics, dancing and/

or martial arts), the frequency (averaged for a week), dura-

tion (averaged in minutes per session) and intensity (strati-

fied as mild physical activity without panting or sweating,

moderate for slight panting or sweating and vigorous for

panting or profuse sweating).

The Chinese Beck Depression Inventory (CBDI)-II was

used to measure depression because of its good reliability

and validity (Chang 2005). The first edition of the BDI was

created by Beck et al. in 1961 and updated in 1996 (the

second edition). There are 21 questions, scored on a Likert

scale of 0–3 for each question, with a total score of 63. A

higher score indicates more severe depression (Chen 2000).

Cronbach’s a in the present study was 0�88, which indi-

cated a high internal consistency. A total score of � 12

was used as the threshold, as this point indicates prominent

depression (Su et al. 2007).

The Chinese Beck Anxiety Inventory (CBAI) was applied

to measure anxiety in the past 2 weeks. The original BAI

was developed by Beck et al. in 1988. It has 21 questions

and is scored on a Likert scale of 0–3 for each question, for

a total score ranging 0–63. A higher score indicates more

severe anxiety (Lin 2000). The CBAI has good reliability

and validity, and a total score of 14 was used as a thresh-

old, because a score of � 14 indicates obvious anxiety

(Che et al. 2006). Cronbach’s a in the present study was

0�9.

Data collection

Data were collected through questionnaires, clinical

records, direct measurements and blood tests. Approval

from the Institute Review Board (IRB) of two research

institutions (Wan Fang and Far Eastern Memorial Hospi-

tals) was acquired before the start of the present study.



C-C Tsai et al.

Individuals were approached prior to their catheterisation,

and the aims and methodology of the present study were

explained to them. Any questions or concerns were clarified

before subjects were catheterised. Blood was collected by

the cardiac catheterisation staff and sent for testing with

participants’ signed consent. Questionnaires were completed

by subjects or researchers if subjects were willing to answer

questions during admission. WC and HC were then

measured. In total, 60–120 minute was required. During

data collection, environmental disturbances were kept to a

minimum. Short rests were granted at any point during

the period. Clinical records were completed by filling in

the catheterisation-related data when subjects were

discharged.

Statistical analysis

Data were input into Microsoft Excel 2007. Outlier values

were then tested with box plots, Z scores and DFBetas.

Statistical analyses were conducted with SPSS 20.0. General

characteristics and the occurrence of RFs were described

using parameters of the number of subjects, percentages,

mean values and standard deviations. Group differences

were tested using chi-squared tests (but Fisher’s exact tests

were used if the predicted value was < 5) and Mann–

Whitney U-tests. RFs for CAD in middle-aged women

were analysed with enter method of a multiple logistic

regression analysis: the Hochberg procedure of multiple

testing to control false discovery rate (Verhoeven et al.

2005). Two-tailed t-tests were used, and statistical signifi-

cance was defined as a p value of < 0�05.

Results

Basic characteristics of subjects

There were 65 subjects in the present study with an aver-

age age of 56�2 years. The majority of participants were

married, and their spouses were still alive (73�8%). Post-

menopausal women comprised 63�1%, and unemployed

persons represented 64�6% of the cohort. In regard to

past medical history, 29�2% had DM, 49�2% had HTN,

40% had dyslipidaemia and 27�7% had a family history

of heart disease. By comparing the general characteristics

between the CAD and control groups, it appeared that

the CAD group had a higher percentage with a DM his-

tory (41�9% vs. 17�6%; v2 = 4�62; p = 0�03) and a lower

percentage of dietary supplementation use in the past year

(25�8% vs. 55�9%; v2 = 6�04; p = 0�01). Furthermore,

there was a borderline effect between the two groups in

terms of HTN and family history. Apart from these, there

was no difference between the two groups in other

variables (Table 1).

Metabolic and biomarker factors

The FBG (130�9 � 52�1 vs. 103�1 � 20�9 mg/dl; Z = 2�51;p = 0�01) and DBP (82�6 � 15�3 vs. 76�5 � 10�9 mmHg;

Z = 2�2; p = 0�03) were significantly higher in the CAD

group compared to their counterparts in the control group.

Levels of TG, LDL, TC, hsCRP and leptin and the measured

values of SBP, BMI, WC and WHR of the CAD group were

higher than those of their counterparts in the control group,

but did not reach statistical significance (Table 2).

Lifestyle factors

Regarding levels of physical activity, 17 subjects (26�6%)

had not engaged in exercise in the past 2 weeks outside of

work and daily activities. The percentage of inactive people

in the CAD group was higher than that of the control

group (40% vs. 14�7%; v2 = 5�23; p = 0�02). Among 47

subjects who engaged in physical activity, there were no

significant differences between the two groups in terms of

frequency, duration and intensity of activity. On the whole,

55 subjects (84�6%) did not smoke, 26�6% were exposed

to SHS in the family, 9�4% were exposed to SHS in the

workplace, 58 subjects (84�1%) had not consumed alcohol

in the past 2 weeks, and there were no statistical differ-

ences between the two groups. Regarding diet, the CAD

group had a higher intake of cholesterol and a higher SFA

ratio; therefore, the proportion of people with an inade-

quate diet in the CAD group was higher than that of the

control group. However, this difference was not statistically

significant. Based on total scores from the CBDI-II and

CBAI evaluations, participants in the CAD group tended to

have a higher prevalence of depression and anxiety

compared to the control group, but these differences were

statistically insignificant (Table 3).

Predictors of CAD

According to the univariate analysis, there were statistical

differences between the two groups in terms of DM, dietary

supplementation use, FBG, DBP and physical activity. Tak-

ing these variables as independent variables, the multiple

linear regression analysis showed that the variance inflation

factor was < 1�5, indicating that there was no collinearity

between the independent variables and assumption that

met. Taking the occurrence of CAD as the dependent




variable and using a multiple logistic regression analysis, it

was demonstrated that dietary supplementation and physi-

cal activity were significant RFs (p < 0�05). Goodness of fit

of overall model was good (Hosmer and Lemeshow test

v2 = 9�38, p = 0�31). After adjusting for other factors, the

probability of occurred CAD in subjects with dietary sup-

plementation use was 0�28 (OR = 0�28; p = 0�04) and the

probability of occurred CAD in subjects who engaged in

physical activity was 0�16 (OR = 0�16; p = 0�02) (Table 4).

Discussion

The present study found that there were significant differ-

ences between the CAD and control group in terms of die-

tary supplementation use, DM, DBP, FBG and engaging in

physical activity. After adjusting for other factors, it was

found that dietary supplementation use and engaging in

physical activity could dramatically reduce the risk of

occurred CAD.

Table 1 Characteristics of subjects

Characteristics Total (n = 65) CAD group (n = 31) Control group (n = 34) v2/Z p-value

Age (years) 56�2 � 6�2 56�0 � 5�5 56�3 � 6�8 �0�47 0�64Years of education 9�0 � 4�1 8�7 � 3�7 9�1 � 4�5 �0�54 0�59Marital status

Married with spouse alive 48 (73�8) 25 (80�6) 23 (67�6) 1�42 0�23Other 17 (26�2) 6 (19�4) 11 (32�4)

Menopausal status

Pre- or perimenopausal 12 (18�5) 5 (16�1) 7 (20�6) 1�75 0�42Postmenopausal 41 (63�1) 22 (71�0) 19 (55�9)Posthysterectomy 12 (18�5) 4 (12�9) 8 (23�5)

Employed

Yes 23 (35�4) 9 (29�0) 14 (41�2) 1�05 0�31No 42 (64�6) 22 (71�0) 20 (58�8)

History of medical conditions

Diabetes

Yes 19 (29�2) 13 (41�9) 6 (17�6) 4�62 0�03*No 46 (70�8) 18 (58�1) 28 (82�4)Hypertension

Yes 32 (49�2) 19 (61�3) 13 (38�2) 3�45 0�06No 33 (50�8) 12 (38�7) 21 (61�8)Dyslipidaemia

Yes 26 (40�0) 13 (41�9) 13 (38�2) 0�09 0�76No 39 (60�0) 18 (58�1) 21 (61�8)Cerebrovascular accident

Yes 3 (4�6) 3 (9�7) 0 3�45 0�10No 62 (95�4) 28 (90�3) 34 (100)

Renal insufficiency

Yes 2 (3�1) 1 (3�2) 1 (2�9) 0�01 1�00No 63 (96�9) 30 (96�8) 33 (97�1)Gout

Yes 4 (6�2) 0 4 (11�8) 3�89 0�12No 61 (93�8) 31 (100) 30 (88�2)

Hormone replacement therapy

Yes 4 (6�2) 3 (9�7) 1 (2�9) 1�27 0�34No 61 (93�8) 28 (90�3) 33 (97�1)Dietary supplementation use

Yes 27 (41�5) 8 (25�8) 19 (55�9) 6�04 0�01*No 38 (58�5) 23 (74�2) 15 (44�1)Family history of premature CAD

Yes 18 (27�7) 12(38�7) 6 (17�6) 3�59 0�06No 47 (72�3) 19 (61�3) 28 (82�4)

*p < 0�05.Values are the mean � SD or number (percentage). Mann–Whitney U-test for continuous variables and chi-squared test for categorical

variables (if cells had an expected count of fewer than 5 for Fisher’s exact test).



C-C Tsai et al.

The percentage of supplement use in the CAD group was

significantly lower than that in the control group (25�8%vs. 55�9%). Among the supplements, multivitamins

(21�9%), B-complex factors (20�3%), Ca and/or vitamin D

(10�9%) were most commonly used. This is similar to the

findings of national surveys in the United States (2003–

2006) (Bailey et al. 2011) and Taiwan (1993–2002) (Chen

et al. 2008). In addition, older females with a higher educa-

tional level used supplements more often. However, the

percentage of people who used supplements among middle-

aged women in Taiwan was 30% lower than that in the

United States (60%).

To date, there are inconsistent findings in the literature

regarding the preventive effects of dietary supplementation

on CAD. It was reported that oxidised LDL plays an

important role in the pathogenesis of atherosclerosis. The

use of vitamins C, E and other antioxidants can reduce

lipid peroxidation and damage caused by free radicals,

therefore exerting a protective effect on cardiac blood ves-

sels (Tinkel et al. 2012). Furthermore, it was shown in two

meta-analyses that vitamin C intake (500 mg/day) for more

than 4 weeks can significantly reduce blood levels of LDL,

TC and TG (McRae 2008). However, daily vitamin E

intake of 50–800 IU did not reduce the incidence or the

mortality rate from CVD (Vivekananthan et al. 2003). Ca

and vitamin D are used by females to prevent osteoporosis.

However, it was shown that a daily Ca intake of > 500 mg

can significantly increase the incidence or mortality rate of

CHD (Bolland et al. 2010). It was reported that a lack of

vitamins B6 and B12 and folate can increase the blood level

of Hcy, which results in oxidative damage to blood vessel

endothelia, lowers NO levels, alters platelet activity and

consequently increases the risk of developing CAD (Lonn

2007). However, the results from a meta-analysis showed

that supplementation with vitamin B6 (> 0�06 mg/day),

vitamin B12 (> 50 mg/day) and folate (> 0�5 mg/day) did

not significantly prevent CHD (Miller et al. 2010). This dis-

crepancy might have been due to differences in dosage and

frequency.

Dietary supplementation may reflect individual awareness

and attitudes towards health. Conner et al. (2001) pointed

out that females decide to use supplements mainly due to

their perceived vulnerability to certain diseases and atti-

tudes towards the benefits of such supplements for health.

It was reported that the majority of middle-aged women

who take supplements have a reduced incidence of smoking

and obesity, and they believe it is important to follow

healthy dietary advice (Archer et al. 2005, Sebastian et al.

2007). It can be extrapolated from the above findings that

supplement users usually have a heightened awareness of

health and are willing to participate in activities that can

prevent diseases or promote health. This seems to explain

why the control group had a higher proportion of supple-

ment use. This behaviour may be due to a heightened

awareness of health, increased cognisance of changes in

physical health, a lower threshold for seeking medical

Table 2 Metabolic and biomarker parameters in subjects by group

Variables

Total (n = 65)

Mean � SD

CAD group (n = 31)

Mean � SD

Control group (n = 34)

Mean � SD Z p-value

FBG (mg/dl) 116�5 � 41�4 130�9 � 52�1 103�1 � 20�9 2�51 0�01*SBP (mmHg) 133�5 � 20�2 136�3 � 24�1 130�9 � 15�8 0�55 0�59DBP (mmHg) 79�4 � 13�4 82�6 � 15�3 76�5 � 10�9 2�20 0�03*TG (mg/dl) 128�8 � 62�5 139�7 � 74�4 118�6 � 47�8 0�78 0�44HDL (mg/dl) 48�6 � 12�4 47�7 � 13�4 49�5 � 11�5 �1�20 0�23LDL (mg/dl) 114�1 � 30�9 117�4 � 32�9 110�1 � 28�6 0�57 0�57HDL/LDL ratio 0�45 � 0�19 0�42 � 0�17 0�49 � 0�21 �1�41 0�16TC (mg/dl) 188�4 � 45�1 193�4 � 36�1 183�8 � 52�1 0�48 0�63BW (kg) 65�3 � 11�9 64�5 � 12�8 66�0 � 11�3 �0�73 0�47BMI (kg/m2) 26�6 � 4�9 26�7 � 5�4 26�6 � 4�5 �0�34 0�73WC (cm) 88�0 � 11�6 88�3 � 12�9 87�7 � 10�5 0�03 0�98HC (cm) 99�4 � 9�9 99�0 � 10�6 99�8 � 9�5 �0�32 0�75WHR 0�88 � 0�06 0�89 � 0�07 0�88 � 0�06 0�42 0�67hsCRP (mg/dl) 0�39 � 1�26 0�68 � 1�79 0�13 � 0�17 1�15 0�25Hcy (lmol/l) 8�7 � 3�1 8�6 � 3�1 8�7 � 3�1 0�15 0�88Leptin (ng/ml) 20�3 � 21�9 20�4 � 20�1 20�3 � 23�9 0�74 0�46

*p < 0�05.FBG, fasting blood glucose; SBP, systolic blood pressure; DBP, diastolic blood pressure; TG, triglycerides; HDL, high-density lipoprotein;

LDL, low-density lipoprotein; TC, total cholesterol; BW, body weight; BMI, body mass index; WC, waist circumference; HC, hip circumfer-

ence; WHR, waist/hip circumference ratio; hsCRP, high-sensitivity C-reactive protein; Hcy, homocysteine.




advice and a higher willingness to accept medical advice in

order to undergo invasive testing to confirm diagnoses.

The present study showed that physical activity was an

important prognostic factor for CAD, and this is consistent

with previous findings. Schnohr et al. (2002) pointed out in

their generational study that inactivity, DM, smoking and

HTN are significant RFs for CAD in females. Although

DM, FBG and DBP significantly differed between the two

groups in the present study and HTN had a borderline

effect according to the univariate analysis, these parameters

did not statistically differ in the multivariate analysis. Physi-

cal activity was shown to be the most important RF, and

this might have been due to a lack of current smokers, the

relatively young age of the subjects (and therefore a shorter

Table 3 Lifestyle variables of subjects by group

Variables Total (n = 65) CAD group (n = 31) Control group (n = 34) 2/Z p-value

Smoking

Never 55 (84�6) 27 (87�1) 28 (82�4) 0�28 0�74Ever 10 (15�4) 4 (12�9) 6 (17�6)

Second-hand smoke (SHS)

SHS at home

No 47 (73�4) 22 (71�0) 25 (75�8) 0�19 0�78Yes 17 (26�6) 9 (29�0) 8 (24�2)SHS at work

No 58 (90�6) 31 (96�8) 28 (84�8) 2�68 0�20Yes 6 (9�4) 1 (3�2) 5 (15�2)

Alcohol intake (g/day) 2�4 � 16�4 0�2 � 0�8 4�4 � 22�7 �0�67 0�500 53 (84�1) 26 (86�7) 27 (81�8) 0�97 1�000�1–12 9 (14�3) 4 (13�3) 5 (15�2)> 12 1 (1�6) 0 1 (3�0)

Dietary intake

Adjusted cholesterol intake (mg/day) 149�6 � 80�8 155�7 � 76�2 145�7 � 84�6 0�66 0�51< 150 32 (61�5) 13 (59�1) 19 (63�1) 0�10 0�76> 150 20 (38�5) 9 (40�9) 11 (36�7)Adjusted saturated fatty acid intake (%) 9�6 � 7�4 10�6 � 10�1 8�8 � 4�6 �0�06 0�96< 7 20 (38�5) 9 (40�9) 11 (36�7) 0�10 0�76> 7 32 (61�5) 13 (59�1) 19 (63�3)Inadequate dietary intake

No 35 (67�3) 14 (63�6) 21 (70�0) 0�23 0�63Yes 17 (32�7) 8 (36�4) 9 (30�0)

Physical activity

Status of physical activity

Inactive 17 (26�6) 12 (40�0) 5 (14�7) 5�23 0�02*Active 47 (73�4) 18 (60�0) 29 (85�3)Frequency (times/week) 3�9 � 2�3 4�5 � 2�1 3�6 � 2�4 1�44 0�15Duration (minute/time) 46�1 � 33�1 48�3 � 43�5 44�7 � 25�4 �0�82 0�41Intensity

Mild 7 (15�6) 2 (11�8) 5 (17�9) 0�78 0�75Moderate 28 (62�2) 12 (70�6) 16 (7�1)Vigorous 10 (22�2) 3 (17�6) 7 (25�0)

CBDI-II score (0–63) 9�0 � 9�1 10�5 � 11�0 7�6 � 6�7 0�87 0�39< 12 46 (73�0) 21 (70�0) 25 (75�8) 0�26 0�61� 12 17 (23�0) 9 (30�0) 8 (24�2)

CBAI score (0–63) 10�4 � 10�4 10�9 � 9�6 9�9 � 11�1 0�62 0�54< 14 48 (75�0) 20 (66�7) 28 (82�4) 2�09 0�15� 14 16 (25�0) 10 (33�3) 6 (17�6)

*p < 0�05.BDI-II, Chinese Beck Depression Inventory-II; BAI, Chinese Beck Anxiety Inventory.

Inadequate diet was adjusted for cholesterol intake > 150 mg and saturated fatty acid intake > 7%. Values are the mean � SD or number

(percentage). Mann–Whitney U-test for continuous variables and chi-squared test for categorical variables (if cells had an expected count of

fewer than 5 for Fisher’s exact test).



C-C Tsai et al.

pathological history) and a paucity of blood glucose and

blood pressure abnormalities. Nonetheless, physical activity

should be emphasised in order to prevent CAD in middle-

aged women.

A national survey in Taiwan conducted in 2009 showed

that 57�5% of middle-aged women had engaged in physical

activity in the previous 2 weeks, which was similar to the

percentage of the CAD group in our study (60%) (Depart-

ment of Health, Executive Yuan 2012b), indicating that

CAD subjects are no less active compared to the general

population. In contrast, the control group had a relatively

higher proportion of people who engaged in physical activ-

ity (85�3%). Physical activity can reduce the incidence of

CAD by improving the function of blood vessel endothelia,

reducing inflammatory factors and lowering blood pressure,

lipids and other metabolic factors (Bowles & Laughlin

2011). Two meta-analyses demonstrated that moderate and

vigorous physical activity can reduce the incidence of CAD

by 20–40% compared to mild activity among females

(Sattelmair et al. 2011, Li & Siegrist 2012). The present

study showed that physical activity could reduce the incidence

of CAD by 84% (OR = 0�16, 95% CI = 0�04–0�70), which is

consistent with the literature findings, although the seemingly

protective effect was much higher in our study. There are

three possible reasons for this: (1) differences in study design,

subjects, assessment tools and categorisation of physical

activity, as adopted by specific studies, might have influenced

the predicted value of the CAD incidence and (2) previous

studies showed that younger females benefited more from the

protective effects of physical activity on the cardiovascular

system compared to older females (Manson et al. 2002). In

the present study, subjects were all middle aged. However,

this relatively younger population of females with CAD may

have been responsible for the pronounced protective effects of

physical activity in this group. (3) The literature indicated that

exercise capacity of patients with CAD might decrease

because of impaired ventricles systolic function (Morrison

et al. 1991), inferring that limiting symptom might lead to

curtailed physical activity habit. The LV ejection fraction

(LVEF) of CAD group was lower than that of control group

in this study (65�4 � 10�1 vs. 71�3 � 7�5%, Z = �1�95,p = 0�05), which resulted in that patients with CAD less fre-

quently perform physical activity or do physical activity of

lower strength. The discrepancy between the two groups was

then enlarged, disclosing the high benefit of performing physi-

cal activity.

It was shown that such protection is dose dependent.

Indeed, the AHA recommends that adults engage in 30 min-

ute of moderate physical activity at least 5 days a week or

at least 20 minute of vigorous physical activity 3 days per

week or 10 minute or more of a combination of moderate

and vigorous physical activity. This latter regime needs to

reach recommended doses through accumulating physical

activity time (Haskell et al. 2007). Another study reported

that for females with CAD, even with physical activity lev-

els not meeting AHA guidelines, there was still a reduction

in mortality in the patient population (Moholdt et al.

2008). It was reported that the protective effects of physical

activity on the cardiovascular system are dose dependent

(Manson et al. 2002). Therefore, sufficient activity within

the recommended range will have greater benefits. How-

ever, activity of any degree will significantly reduce the inci-

dence of CAD compared to being sedentary. The present

study supports the conclusion of Sattelmair et al. (2011)

that ‘some physical activity is better than none’.

Furthermore, the present study found that DM and FBG

were related to CAD. It was shown in a meta-analysis that

DM is an important RF for females (Huxley et al. 2006).

High blood glucose can produce glucotoxicity, oxidative

stress and inflammation, damage the endothelia, increase

thrombin generation and activate platelets. These factors

result in a higher incidence of CAD (Pistrosch et al. 2011).

In the univariate analysis of the present study, a higher pro-

portion of subjects in the CAD group had a DM history

with increased FBG (p < 0�05) during admission. This is

similar to previous findings, but the relationship was no

longer significant when included in the multivariable analy-

sis in the present study.

Table 4 Predictors of coronary artery disease by multiple logistic

regression

Variables B SE Wald p-value

n = 65

OR 95% CI

Constant �4�49 2�27 3�90 0�05 0�01History of

diabetes

(yes vs. no)

0�46 0�79 0�34 0�56 1�58 0�34–7�43

Dietary

supple-

mentation

(yes vs. no)

�1�29 0�63 4�18 0�04* 0�28 0�08–0�95

Fasting blood

glucose (mg/dl)

0�03 0�01 3�31 0�07 1�03 1�00–1�06

Diastolic

blood pressure

(mmHg)

0�04 0�03 2�55 0�11 1�04 0�99–1�10

Physical

activity

(activity vs.

inactivity)

�1�84 0�75 6�00 0�02* 0�16 0�04–0�70

*p < 0�05.




Limitations

This study adopted a cross-sectional, comparative design

and could not demonstrate the causal relationships

between RFs such as dietary supplementation and physical

activity with CAD. Subjects in this study were middle-

aged women. Differences in gender and age will confound

physiological changes and lifestyles; therefore, the present

results cannot be extrapolated to males or females of

other age groups. All subjects were catheterised after

admission. Even though the control group had normal

test results, they may have had mild symptoms. There-

fore, RFs may differ by degree, and this may have led to

the insignificant differences between the two groups in

terms of various RFs. As a result, RF influences were

likely underestimated. Although specific RFs for women

who were receiving hormone treatment or were postmen-

opausal were considered in this study, other conditions

included in the 2011 AHA amendment such as preg-

nancy-related complications (pre-eclampsia, gestational

DM and gestational HTN) and systemic autoimmune dis-

eases (Mosca et al. 2011) were not analysed in this study.

We recommend that such additions be included in future

research. Furthermore, larger study populations of differ-

ent genders and ages from communities should be encour-

aged in investigation to ensure comprehensive assessment

of RFs.

Conclusions

Dietary supplementation use and physical activity among

middle-aged women in Taiwan can predict the incidence of

CAD after adjusting for DM history, FBG, DBP and other

RFs. The protective effect of supplement use might be

related to the positive attitudes of such users who demon-

strate a heightened awareness of their health. This study

supports the idea that engaging in some physical activity is

better than nothing. We encourage busy middle-aged

women to undertake at least some physical activity, no

matter how close such activity reaches recommended

amounts. Indeed, there are benefits associated with any

physical activity.

Relevance to clinical practice

Coronary artery disease has become the main cause of

female mortality. Controlling RFs for CAD can effectively

prevent the development of CAD and death. The impor-

tance of various RFs is affected by gender, ethnicity and

lifestyle. Understanding RFs for CAD in females will reduce

the cost of prevention and treatment of CAD and improve

the efficacy of such interventions. Emphasis should be

placed on CAD prevention by healthcare workers and the

general public. It is clear that supplement use and physical

activity can significantly predict CAD; therefore, middle-

aged women are encouraged to take appropriate supple-

ments and engage in physical activity in order to prevent

CAD.

Acknowledgements

This study was supported by NSC 98-2314-B-038

-021 -MY3.

Contributions

Study design: CCT, CJ; data collection and analysis: CCT,

MHH, PLC, CJ, AHL and manuscript preparation: CCT, CJ.

Conflict of interest

None.

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