Prevention of Cardiovascular Disease in Woman

MOH/P/PAK/171.
08(GU)
STATEMENT OF INTENT
This guidelines was developed to be a guide for best clinical practice
for the prevention of cardiovascular diseases in women, based on
the best available evidence at the time of development. Specific
attempts were made to use local data and publications to ensure
local relevance. Adherence to this guidelines does not necessarily
lead to the best clinical outcome in individual patient care. Every
health care provider is responsible for the management of his/her
unique patient based on the clinical presentation and management
options available locally.
REVIEW OF THE GUIDELINES

This guidelines is issued in 2008 and will be reviewed in 2013 or
earlier if important new evidence becomes available.
CPG Secretariat
Health Technology Assessment Unit
Medical Development Division
Level 4, Block EI, Parcel E
Government Offices Complex
62590 Putrajaya, Malaysia
Available on the following websites:

http://www.moh.gov.my
http://www.acadmed.org.my
MESSAGE FROM THE DIRECTOR GENERAL OF HEALTH

Women account for 49.7% of the Malaysian population. Therefore
it is not surprising to note that with the advances in medicine, there
are increasing instances of diseases or presentations that are more
unique to women.
With increasing and longer life expectancy of 76.4 years in the
Malaysian women, cardiovascular disease will become not only
the most common morbidity and mortality for women in Malaysia
but with increasing frequency.
Established CPG provides important guidance to the health care
professional, however it will only be of value if it is translated
into practice. I am pleased to note that this CPG provides for
comprehensive primary as well as secondary prevention and
management for women with cardiovascular disease in the
Malaysia setting.
Lastly, I would like to congratulate the CPG writing committee for
their personal dedication and sacrifice in time which was well spent
to help ensure that the women of our nation will have a healthier
heart.
Y.Bhg Tan Sri Datuk Dr Hj Mohd Ismail Merican

Director General of Health Malaysia
II
MEMBERS OF THE EXPERT PANEL

Chairperson:
Dr Robaayah Zambahari
Senior Consultant Cardiologist

Institute Jantung Negara, KL
Secretary:
Dr Jeyamalar Rajadurai
Consultant Cardiologist
Subang Jaya Medical Centre,
Selangor
Expert Panel Members (in alphabetical order):
Dr Chan Siew Pheng
Senior Consultant Endocrinologist

University Malaya Medical Centre, KL
Dr Ong Mei Lin
Consultant Cardiologist
Gleneagles Medical Centre, Penang
Dr Santha Kumari
Senior Consultant Physician

Hospital Tengku Ampuan Rahimah,
Selangor
Dr Sim Kui Hian
Senior Consultant Cardiologist

Sarawak General Hospital, Sarawak
Dr Zanariah Hussein
Consultant Endocrinologist
Hospital Putrajaya, Putrajaya
III
External Reviewers:
Dr Aris Chandran
Dr Chia Yook Chin
Dr Fatanah Ismail
Dr Majdah bt Hj Mohamed
Dr Lee Fatt Soon
Dr Husni Hussain
Consultant Physician
Ipoh General Hospital
Perak
Principle Assistant Director and
Epidemiologist
Disease Control Division
Ministry of Health Malaysia
Putrajaya
Consultant Geriatrician
Hospital Kuala Lumpur
Kuala Lumpur
Consultant Physician
University Malaya Medical Centre
Kuala Lumpur
Principal Assistant Director
Womens Health Department
Public Health Division
Ministry of Health Malaysia
Putrajaya
Family Medicine Specialist
Klinik Kesihatan Putrajaya,
Putrajaya
Dr Mukudan Krishnan
Consultant Obstetrics & Gynaecology
Ipoh General Hospital
Perak
COMMENTS FROM INTERNATIONAL REVIEWERS:
"My congratulations on an extremely well done Guideline

on CVD Prevention in Women - you have done an excellent
job in incorporating both U.S. and European parameters."
Nanette K. Wenger, M.D.
Professor of Medicine in the Division of Cardiology at

the Emory University School of Medicine
Chief of Cardiology at Grady Memorial Hospital
Consultant to the Emory Heart and Vascular Center
"These are wonderful - so well formatted and wonderful

production."
C Noel Bairey Merz, M.D., F.A.C.C., F.A.H.A.
Director Women's Heart Center

Director Preventive and Rehabilitative Cardiac Center Women's Guild Endowed
Chair in Women's Health Cedars-Sinai Medical Center Professor of Medicine
David Geffen School of Medicine at UCLA
IV
RATIONALE AND PROCESS OF GUIDELINE

DEVELOPMENT
Rationale:
Cardiovascular disease (CVD) is an important cause of morbidity
and mortality in Malaysian women. Unfortunately many women and
healthcare professionals have the misconception that CVD is not a
womans disease and that it is a disease that only affect men.
This Clinical Practice Guidelines has been drawn up by a committee
appointed by the National Heart Association of Malaysia, Ministry of
Health and the Academy of Medicine. It comprises of cardiologists,
endocrinologists and general physicians from the government and
private sectors and the Universities.
Objectives:
The objectives of this guidelines are to :
Increase awareness regarding cardiovascular disease in women
among healthcare providers
Improve detection and management of women with cardiovascular
disease
Develop a preventive strategy for cardiovascular disease in
women
Process:
Evidence was obtained by systematic review of current medical
literature on womens health and preventive medicine using the
usual search engines PubMed, Medscape and Ovid. The other
international guidelines (American and European) on Prevention of
Cardiovascular Disease in Women were also studied. After much
discussion, the draft was then drawn up by the members of the
Expert Panel and submitted to the Technical Advisory Committee
for Clinical Practice Guidelines, Ministry of Health Malaysia and key
health personnel in the Major Hospitals of the Ministry Of Health and
the Private Sector for review and feedback.
The clinical questions were divided into major subgroups and
members of the Expert Panel were assigned individual topics. The
group members met several times throughout the development of
the guideline. All literature retrieved were appraised by individual
members and presented and discussed during group meetings.
All statements and recommendations formulated were agreed
collectively by members of the Expert Panel. Where the evidence
was insufficient the recommendations were derived by consensus
of the Panel. The draft was then sent to local external reviewers for
V
comments. It was also sent to members of the American College of

Cardiology and the European Society of Cardiology for feedback.
The level of recommendation and the grading of evidence used in
this guidelines was adapted from the American Heart Association
and the European Society of Cardiology (ACC/ESC) and outlined in
page VIII. In the text, this is written in black in the outer margin. For
the purpose of standardisation with the other Ministry of Health
Clinical Practice Guidelines, we have also used the grading system
of the U.S./Canadian Preventive Services Task Force as outlined in
page IX. This is written in red in the inner margin.
Clinical Questions Addressed:

Are there gender specific differences in the epidemiology of
cardiovascular disease?
Do women with cardiovascular disease present in the same
manner as men?
Are there gender differences in the management of women with
cardiovascular disease?
Are the risk factors for cardiovascular disease different in
women?
How do you prevent cardiovascular disease in women?
Target Group:
This guidelines is directed at all healthcare providers treating
women general practitioners, general and family physicians,
cardiologists, endocrinologists and gynaecologists.
Target Population:
It is developed to prevent cardiovascular disease in all women.
Period of Validity of the Guidelines:

This guidelines needs to be revised at least every 5 years to keep
abreast with recent developments and knowledge that is being
learnt regarding womens health.
Implementation of the Guidelines:

The implementation of the recommendations of a CPG is part of
good clinical governance. To ensure successful implementation of
this CPG we suggest:
Increasing public awareness of cardiovascular disease in general
and educating them on the importance of knowing their individual
cardiovascular risk
VI
Continuous medical education and training of healthcare

providers on methods of cardiovascular risk assessment and
the implementation of appropriate preventative strategies
depending on each individuals risk status
Clinical audit by individual hospitals, units and general practices
to ensure compliance. Suggested audit parameters are as in
the Audit of Clinical Diabetes (Green Book) by the Unit Penyakit
Kardiovaskular dan Diabetes ( see Appendix 5)
Dr Robaayah Zambahari
Chairperson
VII
GRADES OF RECOMMENDATION
I
Conditions for which there is evidence and/or

general agreement that a given procedure/therapy
is beneficial, useful and/or effective.
II
Conditions for which there is conflicting evidence

and/or divergence of opinion about the usefulness/
efficacy of a procedure/therapy.
II-a
Weight of evidence/opinion is in favor of its

usefulness/efficacy.
II-b
Usefulness/efficacy is less well established by

evidence/opinion
III
Conditions for which there is evidence and/or

general agreement that a procedure/therapy is
not useful/effective and in some cases may be
harmful.
LEVELS OF EVIDENCE
Data derived from multiple randomized clinical

trials or meta-analysis
Data derived from a single randomized clinical trial

or large non randomized studies
Only consensus of opinions of experts, case studies

or standard of care
Adapted from the American Heart Association and the European Society of
Cardiology
VIII
KEY TO EVIDENCE STATEMENTS

LEVEL
I
Evidence obtained from at least one properly

randomized controlled trial
II - 1
Evidence obtained from well-designed controlled trials

without randomization
II - 2
Evidence obtained from well-designed cohort or casecontrol analytic studies, preferable from more than
one center or research group
II - 3
Evidence obtained from multiple time series with

or without the intervention. Dramatic results in
uncontrolled experiments (such as the results of the
introduction of penicillin treatment in the 1940s) could
also be regarded as this type of evidence
III
Opinions of respected authorities, based on clinical

experience; descriptive studies and case reports; or
reports of expert committees
Source from U.S./CANADIAN PREVENTIVE SERVICES TASK FORCE
GRADES OF RECOMMENDATIONS
A
At least one meta-analysis, systematic review, or RCT,

or evidence rated as good and directly applicable to
the target population
Evidence from well conducted clinical trials, directly

applicable to the target population, and demonstrating
overall consistency of results; or evidence extrapolated
from meta analysis, systematic review, or RCT
Evidence from expert committee reports, or opinions

and/or clinical experiences of respected authorities;
indicates absence of directly applicable clinical
studies of good quality
Source: Guidelines for CLINICAL PRACTICE GUIDELINES,
Ministry of Health Malaysia, 2003
IX
PREVENTION OF CARDIOVASCULAR
DISEASE IN WOMEN
SUMMARY:
Cardiovascular disease (CVD) is the main cause of death among

women in Malaysia.
In the National Health and Morbidity Survey (NHMS) III, the
prevalence of lifestyle related diseases (hypertension, diabetes,
overweight and obesity) has increased significantly. In addition,
the longer life expectancy of Malaysian women (76.4 years) will
further increase the CVD burden.
Gender differences include the following: Presenting symptoms for CHD and stroke in women may be
atypical.
Women have a higher prevalence of CVD risk factors with
increasing age.
The physiological changes associated with midlife and
menopause contributes to this increased prevalence of risk
factors.
CVD risk factors such as hypertension, diabetes and smoking
confer a worse prognosis in women.
Increased awareness, early and appropriate investigations and
management of CVD is important.
All women should know the levels and significance of their risk
factors. All women above the age of 40 years, should have their
CVD risk assessed and risk stratified to: High Risk
At Risk
Optimal Risk
Assessment of CVD risk involves:
History: Looking for symptoms of CHD or CHD Equivalents,
family history of premature CHD, smoking status, physical
activity
Physical Examination: Height, weight, BMI, waist circumference, pulses, blood pressure
Investigations: Blood sugar, lipid profile
The CVD risk factors should be identified and appropriately
managed to target : High Risk intensive risk factor reduction with pharmacological
and lifestyle changes from the outset.
At Risk non pharmacological intervention with diet and
physical activity. If targets not achieved, pharmacological
therapy is indicated.
Optimal Risk continue with healthy lifestyle measures.
X
INTERVENTIONS TO PREVENT CARDIOVASCULAR

DISEASE IN WOMEN
INTERVENTION
ACC/ESC
Classification
MOH
Classification
General Recommendations to all women

Diet rich in fruits and
vegetables, whole grain,
high fiber food, oily fish,
lean meat, low fat milk
and cheese
Grade I, Level C
Level III, Grade C
Exercise a minimum
of 30mins of moderate
intensity exercises on
most days of the week
Grade I, Level B
Level II-1, Grade B
Maintain BMI 18.5 to

<23kg/m2 and waist
circumference <80cm
Grade I, Level B
Level II-2, Grade B
Stop smoking
Grade I, Level B
Level II-2, Grade B
Treatment of specific risk factors

Lipids:
High Risk:
LDL-C <2.6mmol/l
with an option of

<2.0mmol/l
At Risk:
LDL-C <3.4mmol/l
Optimum Risk:
LDL-C <4.1mmol/l
Hypertension:
<140/85mmHg in most
patients
<130/80mmHg in pts
with CHD, diabetes and
chronic kidney disease
<125/75mmHg in the
presence of proteinuria
XI
Grade I, Level A
Level 1, Grade A
Grade I, Level B
Grade I, Level A
Level 1, Grade A
Grade I, Level A
Level 1, Grade A
Grade I, Level A
Level 1, Grade A
Diabetes:
HBA1c <6.5%
Grade I, Level A
Level 1, Grade A
LDL-C <2.6mmol/l
Grade I, Level A
Level 1, Grade A
TG <1.7mmol/l
BP <130/80mmHg
Grade I, Level A
Level 1, Grade A
Aspirin:
in patients with CVD
Grade I, Level A
Level 1, Grade A
Grade I, Level B
Level 1, Grade A
Grade I, Level A
Level 1, Grade A
Grade I, Level B
Level 1, Grade A
Grade III,Level A
Level 1, Grade A
Grade III,Level A
Level 1, Grade A
primary prevention in
women >65 years
Anticoagulation with
warfarin in AF if:
-heart failure,
impaired LV function,
hypertension, age over
75 years, diabetes
and previous history of
stroke or TIA present
-age between 64 to 75
years, female gender
and coronary artery
disease
Others:
-Anti-oxidants
-Hormone replacement
therapy
XII
TABLE OF CONTENTS
1. THE SCOPE OF THE PROBLEM
2. TYPES OF CARDIOVASCULAR DISEASE

2.1
Coronary Heart Disease
2.1.1
Presenting Symptoms
2.1.2
Risk Factors
2.1.3
Diagnosis
2.1.3.1
Stress Testing
2.1.3.2
Newer Imaging Modalities
2.1.3.3
Coronary Angiography
2.1.4
Management
2.1.5
Unique gender specific cardiac issues
2.1.5.1
Syndrome X
2.1.5.1.1
Management
2.1.5.2
Cardiac arrhytmias
2.1.5.3
Heart failure
2.2
Cerebrovascular Disease
2.2.1
Epidemiology
2.2.2
Presenting symptoms
2.2.3
Risk factors
2.2.3.1
Special issues for Stroke in women
2.2.3.1.1
Oral contraceptive use
2.2.3.1.2
Hormone Replacement Therapy
2.2.3.1.3
Pregnancy
2.2.3.1.4
Migraine
2.2.4
Diagnosis and management
2.3
Peripheral Arterial Disease
2.3.1
Presenting symptoms
2.3.2
Diagnosis
2.3.3
Management
2.4
Aortic Atherosclerosis and Thoracic or

Abdominal Aortic Aneurysm (AAA)
2.4.1
Presenting symptoms
2.4.2
Diagnosis
2.4.3
Management
4
4
4
4
4
5
6
6
6
6
6
7
7
7
8
8
8
8
8
8
9
9
9
9
9
9
9
10
3. CARDIOVASCULAR RISK FACTORS

3.1
Personal history of CHD or CHD

equivalents
3.2
Age
3.3
Family history of premature CHD
3.4
Dyslipidaemia
3.5
Hypertension
3.6
Diabetes mellitus/Pre-diabetes
3.6.1
Diabetes mellitus
3.6.2
Pre-diabetes
3.7
Metabolic Syndrome
3.8
Obesity
3.9
Smoking
3.10
Physical Activity
3.11
Others
12
XIII
10
10
11
11
12
12
13
13
14
16
16
16
17
18
21
21
23
3.11.1
3.11.2
3.11.3
3.11.4
Oral Contraceptives
Hormone replacement therapy
Pre-eclampsia
Alcohol
4. TOTAL CARDIOVASCULAR RISK ASSESSMENT
23
23
24
24
26
5. RECOMMENDATIONS FOR PREVENTION

OF CVD IN WOMEN
5.1
General recommendations
5.1.1
Nutrition
5.1.2
Physical activity
5.1.3
Weight maintenance/reduction
5.1.4
Cigarette smoking
5.1.5
Aspirin
5.2
Treatment of Specific Risk Factors
5.2.1
Dyslipidaemia
5.2.1.1
Targets of therapy
5.2.1.2
Management of Dyslipidemia:

Primary prevention
5.2.1.3
Management of Dyslipidemia:

Secondary prevention
5.2.2
Hypertension
5.2.2.1
Targets of therapy
5.2.2.2
Gender specific issues
5.2.3
Diabetes
5.2.3.1
Targets of therapy
5.2.4
Overweight and obesity
5.2.4.1
Overall goals for weight loss management
5.2.5
Others
33
33
33
33
34
34
35
35
35
REFERENCES
37
APPENDIX 1
APPENDIX 2

APPENDIX 2A
APPENDIX 2B
APPENDIX 2C
APPENDIX 3
APPENDIX 4
APPENDIX 4A
APPENDIX 4B

APPENDIX 4C
APPENDIX 5
Alcohol content of common spirits

Framingham risk score for assessment
of CVD Risk
CVD points for women
CVD risk for women
Heart age/Vascular age for women
Suggested drug therapy for dyslipidaemia
Management of Hypertension
Risk stratification of hypertension
Recommendations for follow
up based on initial BP
Effective anti hypertensive combinations
Audit of clinical diabetes green book
ACKNOWLEDGEMENTS
DISCLOSURE STATEMENT
SOURCES OF FUNDING
30
30
30
31
31
31
31
32
32
32
32
48
49
49
50
50
51
52
52
53
53
54
55
55
55
XIV
1. THE SCOPE OF THE PROBLEM

Cardiovascular disease (CVD) is the main cause of death among
women worldwide. In Malaysia, it is the main cause of death in
women accounting for about 25% of all female deaths in government
hospitals (about 1 in 4)1. (Figure 1A) This trend has remained
unchanged since 19991. Female deaths due to CVD is almost two
and a half times that of deaths due to all cancers combined. More
females died from heart disease than strokes. (Figure 1B)
Figure 1A : Death among women due to Cardiovascular

Disease* and all Cancers Combined * in Malaysia**
(1999 2005)
* expressed as % of total female deaths

** deaths in government hospitals only
Figure 1B: Death among women due to Heart Disease and

Strokes in Malaysia**
** deaths in government hospitals only
These facts are not well appreciated by both the general public and
health care professionals who often regard CVD as a problem that
only affect men.
This lack of awareness has contributed to: failure in providing adequate information and health promotion
to the public regarding CVD in women
less screening for risk factors that contribute to CVD in women
higher threshold for diagnosis and management of these risk
factors
lower rates of diagnosis of CVD in women
lower usage of appropriate medications and interventions for
treating women with CVD
To compound the problem, presenting symptoms in women with
heart disease are often atypical. Some present with breathlessness
and fatigue rather than with typical chest pain. Thus, they are not
appropriately triaged in the emergency room resulting in a delay in
the diagnosis and treatment. This has adverse consequences on
their prognosis.
It is a commonly perceived myth among the general public and
health care professionals that CVD has a more benign course in
women. In fact in-hospital2 and early post myocardial infarction3
(MI) mortality is greater in women than in men (9% vs 4%4). Even
2
after one year, the mortality rate after an MI is 32% higher in women
than in men5.
Similarly, following a stroke, women are more likely to die than men
(16% vs 8%)6. Those who survive have a poorer long term outcome
and a lower quality of life. Stroke is the second most important
cause of death in women7,8. It is the most important cause of
disability9 and the second most common cause of dementia after
Alzheimers disease10 in women.
This Clinical Practice Guidelines (CPG) highlights the important
gender differences in CVD. There are differences in the clinical
presentation, predisposing risk factors and the presence of comorbidity in women. The accuracy of diagnostic tests and physiologic
responses to exercise differ. Cultural norms, socioeconomic and
psychological factors all affect the way women respond to their
illness. These factors all have an impact on the management of
CVD in women.
Cardiovascular disease often strikes without warning, underscoring
the importance of prevention. This CPG provides evidence
based recommendations focusing on preventing CVD in women.
It addresses the impact of the different risk factors on CVD in
women, the role of lifestyle changes and the use of appropriate
drug therapies in the prevention of CVD. However, decision making
should be individualized and based on sound clinical judgment.
2. TYPES OF CARDIOVASCULAR DISEASE

Cardiovascular disease (CVD) includes:
Coronary heart disease (CHD) as manifested by angina pectoris,
MI, heart failure (HF) and coronary death
Cerebrovascular disease manifested as transient ischaemic
attack (TIA) and stroke
Peripheral arterial disease (PAD) manifested as intermittent
claudication and critical limb ischaemia (CLI)
Aortic atherosclerosis and thoracic or abdominal aortic aneurysm.
Although these are manifestations of atherosclerosis, in some
clinical studies, they are not included in the definition of CVD.
2.1 CORONARY HEART DISEASE

2.1.1 Presenting Symptoms
The prevalence of obstructive CHD in women is relatively low
before menopause11. In general, women develop CHD about 10
years later then men11.
Women differ in the characteristics of symptoms at presentation12.
Angina pectoris is an earlier and more common presentation in
women as compared to men who more often present with MI11.
Prodromal symptoms when present, are often atypical eg shortness
of breath, sleep disturbances and fatigue. However, when
presenting as an acute coronary syndrome, women are as likely as
men to present with typical chest pain associated with sweating i.e.
there are no gender differences13.
2.1.2 Risk Factors
There are important gender-related differences in the prevalence
and outcome of cardiac risk factors (refer section 3). Elderly
hypertensive women and young female smokers are especially at
risk for CHD.
2.1.3 Diagnosis
Women with CHD symptoms are less likely to be referred for
appropriate investigations due to the following: patient factors
cultural norms passive nature, fearfulness, anxiety, denial
and self sacrifice
co-morbidity eg arthritis, obesity
age
physician factors
lack of awareness and misconceptions
4
Investigations for diagnosing CHD include non-invasive and

invasive tests. There are important gender differences in the
sensitivity and specificity of the various non-invasive tests.
2.1.3.1 Stress Testing
Conventional stress testing has a lower diagnostic accuracy in
women. The sensitivity and specificity is about 60 to 70% in women
and about 80% in men14. This is partly due to: lower CHD prevalence in pre-menopausal women and thus a
lower pretest probability of disease
poor exercise tolerance resulting in failure to achieve an
adequate level of stress
presence of baseline ECG abnormalities making interpretation
difficult
Despite these limitations, a normal stress ECG at adequate
workloads in women with intermediate probability of CHD is a good
indication that there is no significant obstructive lesion15,16.
Due to the limitations of stress testing, stress echocardiography
(exercise and dobutamine) and stress SPECT17 have been
recommended in women because of the higher specificity. A
proposed algorithm for the investigation of women suspected of
having CHD is as shown in figure 2.
Figure 2: Algorithm for the non-invasive investigation of
women suspected of CHD
2.1.3.2 Newer Imaging Modalities

Computed tomographic (CT) Coronary Calcium scoring, CT
coronary angiography and cardiac magnetic resonance imaging
are newer imaging modalities that maybe helpful in the diagnosis
of CHD in women. However, currently, there is insufficient evidence
to recommend its routine use as a screening tool.
2.1.3.3 Coronary Angiography
Women are less likely to be offered coronary angiography in view
of their atypical symptoms and the lower predictive value of noninvasive testing. When used appropriately, coronary angiography
is associated with a similar low complication rate as compared
to men. Its underutilization in women results in under-diagnosis,
suboptimal treatment and poorer long term outcome.
2.1.4 Management
Evidence based data on the management of CHD in women
are limited because they are generally under represented in the
randomized controlled trials. Available data however, suggests that
most of the benefits seen in men can be extrapolated to women.
Women with CHD should be treated in the same manner and as
aggressively as men.
2.1.5 Unique gender specific cardiac issues
2.1.5.1 Syndrome X
Syndrome X is angina in the absence of obstructive CHD. The
diagnosis is suggested by the triad of anginal-type chest discomfort,
objective evidence of ischemia, and absence of obstructive CHD18.
It should not be confused with the metabolic syndrome, which also
used to be called Syndrome X.
Syndrome X is more common in women than men; about 70% of
patients are women who are approaching or are post menopausal19.
About 60% of women undergoing coronary angiography for chest
pain do not have major obstructive CHD20.
There are several theories on its aetiology.Two factors that may
be involved are:
Microvascular dysfunction. About 50% of women with Syndrome
X have evidence of microvascular dysfunction20, but only about
20% to 25% show signs of ischaemia19,21
Enhanced pain perception22,23,24
6
Patients with Syndrome X generally have a good prognosis, but

often continue to suffer from chest pain even with treatment.
However, women with Syndrome X and severe endothelial
dysfunction have a 30% increased risk of developing CHD at 10
years25.
2.1.5.1.1 Management
This includes:
Nitrates only half of all Syndrome X patients respond to
nitrates18,19 Sometimes the chest pain may also be GTN
resistant18
Calcium channel blockers18,19,26
-blockers18,19,27
2.1.5.2 Cardiac arrhythmias
Women have a lower rate of sudden cardiac death (SCD) than
men28,29,30. The prevalence of CHD, the primary cause of SCD, is
lower in women31. However, even amongst individuals with known
CHD, women are less likely to experience SCD. Gender differences
have been noted in the inducibility of ventricular arrhythmias
among patients with CHD32,33 and in the frequency of non sustained
ventricular tachycardia (VT) in patients with congestive heart
failure34 suggesting that women may have a lower propensity to
ventricular arrhythmias.
However in the CAST study35 two factors significantly increased
the hazard ratio (HR) for arrhythmic death or resuscitated cardiac
arrest in non-randomized patients. These were:
female gender (HR 4.7, p <0.05) and
electrocardiographic abnormalities (such as VT, proarrhythmia,
widened QRS complex, heart block, bradycardia)
Women were also found to be more prone to develop torsades de
pointes during administration of cardiovascular drugs that prolong
cardiac repolarization (QT interval)36.
2.1.5.3 Heart failure
Common aetiologies of heart failure (HF) in women include
hypertension, CHD and valvular heart disease. Left ventricular
diastolic dysfunction is more common in women37,38 due to the
effects of prolonged hypertension and diabetes39. In addition,
women develop CHD and HF later in life and have more agerelated changes in the heart, such as poor diastolic performance
at that time.
The prognosis of women with HF is generally better than that of

men40,41. However if the aetiology of HF is ischaemia related, the
prognosis is similar40.
2.2 CEREBROVASCULAR DISEASE

2.2.1 Epidemiology
Stroke is now the second leading cause of death in women
worldwide, after CHD7,8 and has been projected to remain an
important cause of mortality till 20208. Data from the United States
National Health and Nutrition Examination Survey (NHANES)
showed that women in the age group 45 to 54 were twice as likely
as men the same age to suffer strokes42. The incidence rates were
similar between the gender for the age groups 35 to 44 and 55 to
64 years. From 1999 to 2004 in the United States, the incidence of
strokes increased in women but decreased in men.
2.2.2 Presenting symptoms
There are significant differences in the way women and men
with stroke present. Women were more likely to report vague
sensations not classical of stroke. In particular, women were more
likely to report pain, changes in consciousness or disorientation
or non-neurological symptoms such as shortness of breath and
chest pain. As a consequence of this, women do not get treatment
as quickly as men.
2.2.3 Risk factors
Women and men share many common risk factors for stroke. These
include the common risk factors for CVD discussed in section 3, as
well as other stroke risk factors such as : atrial fibrillation
carotid artery disease
transient ischaemic attacks
family history of premature stroke
previous history of stroke
2.2.3.1 Special issues for Stroke in women
Women also face additional gender-specific risk factors. These
include: oral contraceptive use 43,44
hormone replacement therapy45
pregnancy
migraine
2.2.3.1.1 Oral contraceptive use (refer Section 3.11.1)
8
2.2.3.1.2 Hormone Replacement Therapy (refer Section 3.11.2)

2.2.3.1.3 Pregnancy
Pregnancy increases the risk of a stroke in women due to:
pregnancy induced hypertension
increased blood coagulability
postpartum haemorrhage with hypotension
The incidence of stroke, both ischaemic and hemorrhagic, is
markedly increased in the postpartum period.
2.2.3.1.4 Migraine
Women are more likely to suffer from migraine. Migraine increases
the risk of stroke in young women46,47.
Women with migraine and visual aura are more likely to develop
ischaemic stroke. This risk is higher in current cigarette smokers
and current users of oral contraceptives48.
2.2.4 Diagnosis and management
There are no gender differences in the way strokes are diagnosed
and managed. Please refer to Malaysian CPG on Management of
Stroke (2006).
2.3 PERIPHERAL ARTERIAL DISEASE

The prevalence of PAD in women is similar to that of men and
ranges from 3%-29%49. In women, PAD tends to be asymptomatic.
Women with PAD, whether symptomatic or asymptomatic, tend
to have poorer prognosis. They have an increased risk of MI,
cardiovascular and total mortality49,50,51.
2.3.2 Diagnosis
A history of intermittent claudication49 is often absent in women with
PAD. Measurement of the ankle-brachial index using a Doppler
ultrasound, detects about 3-5 times more cases than history alone49.
The following women, symptomatic and asymptomatic, should be
screened for PAD52,53 :
those with exertional leg symptoms
the elderly (above the age of 70 years)
those above the age of 50 years with any atherosclerotic risk
factor (smoking, diabetes, hypertension, elevated cholesterols)
diabetics who are 49 years old or younger or who have any of

these atherosclerotic risk factors
subjects with a 10 year CVD risk of 10-20% (Framingham risk
score)
These women should be screened by history and clinical
examination of the foot pulses. The diagnosis of PAD may be
objectively confirmed by the measurement of the ankle brachial
index (ABI) by Doppler ultrasound. The presence of PAD
indicates a high risk individual and alters the intensity of risk factor
modification.
2.3.3 Management
Patients with intermittent claudication should undergo a supervised
exercise program54. Treatment options include medical therapy,
angioplasty and surgery.
A phosphodiesterase III inhibitor (cilostazol) has been shown to
improve exercise performance and quality of life in symptomatic
patients55. Statins have also been shown to be beneficial56,57.
Patients with PAD whether symptomatic or not, should be treated
as aggressively as patients with CHD with risk factor modification,
anti-platelet agents (aspirin or clopidogrel58), statins59, -blockers
and angiotensin-converting enzyme inhibitors (ACEI)60.
The use of -blockers have previously been discouraged in
the presence of PAD because of the possibility of worsening
limb ischaemia. However a meta-analysis has shown that these
drugs can be safely used in stable patients with mild to moderate
symptoms of PAD61. A more recent review showed that -blockers
do not decrease ABI at rest, calf blood flow at rest and after exercise
although it did worsen claudication distance62.
Level I, Thus the presence of stable PAD is not
Grade A use of -blockers in patients with CHD.
a contraindication for the Grade I,

Level A
2.4 AORTIC ATHEROSCLEROSIS AND THORACIC OR

ABDOMINAL AORTIC ANEURYSM (AAA)
Aortic atherosclerosis is usually asymptomatic and was noted in
38% of women63.
Aortic aneurysms are uncommon in women. The prevalence
10
ranges from 0.6 to 1.4% which is about 15% of that seen in men.
Women present seven to ten years later than men64. Most AAArelated deaths occur before 80 years of age in men and after 80
years of age in women64.
2.4.2 Diagnosis
There is no evidence that routine screening is beneficial in women.
If an aortic aneurysm is suspected diagnostic tests include
ultrasound, CT scan and MRI64.
2.4.3 Management
The goal of management of aortic aneurysms is to prevent rupture.
This involves aggressive risk factor control, adequate -blockade
and serial imaging for progression.
The general guidelines for the management of abdominal aortic
aneurysms are:
Small aneurysm (4cm or smaller)
Conservative therapy with periodic ultrasound examinations
to assess progression
Medium sized aneurysm (between 4cm and 5.5cm)
Treatment of these are still unclear. Closer and more frequent
monitoring for progression is recommended
Large (5.5cm or larger), fast-growing aneurysm (more than
0.5cm over six months) or symptomatic (leaking, tender or
painful)
Surgical or endovascular repair is recommended
Key Messages:
Cardiovascular disease is the main cause of death in women
in Malaysia
Presenting symptoms for CHD and stroke in women may be
atypical
Prognosis for women following an MI and stroke is poorer
than men
Increased awareness, early detection with appropriate
investigations and management is important
11
3. CARDIOVASCULAR RISK FACTORS

Important cardiovascular risk factors in women include:
a) Non-modifiable risk factors
personal history of CHD and/or CHD equivalents
age (over 55)
family history of premature CHD
b)
Modifiable risk factors

dyslipidaemia
hypertension
diabetes mellitus/pre-diabetes
metabolic syndrome
obesity
smoking
physical inactivity
3.1 PERSONAL HISTORY OF CHD AND/OR CHD

EQUIVALENTS
Women with established CVD are at high risk for recurrent vascular
events. This includes women with:
CHD and/or
CHD risk equivalents which are: cerebrovascular disease
peripheral arterial disease
diabetes mellitus
multiple risk factors that confer a 10 year Framingham Risk
Score (FRS) of >20%65 or a SCORE risk of >5%66 or WHO/
ISH risk of >30%67
The presence of vascular disease in any one of the vascular beds
usually indicates co-existing disease in other parts of the vascular
tree. Hence it is imperative to assess all vascular beds.
3.2 AGE
The age-specific incidence rates for CHD in women are lower than
in men at every age68,69. The onset of CHD may be delayed by
about 10 years in women11.
Atherosclerosis starts in early adolescence and progresses
throughout a womans lifetime, the rate of progression depending
upon the presence and severity of the risk factors. In mid life, a
womans risk for CVD increases dramatically. This is due to: the effect of increasing age, an effect that is also similarly
observed in men
12
the hormonal imbalances that occur with the menopause, and

an increase in the prevalence of risk factors for heart disease
often seen in mid life such as: obesity and changes in body fat distribution from a gynaecoid
(subcutaneous fat) to an android (abdominal obesity) pattern
physical inactivity
dyslipidaemia
hypertension
worsening glucose tolerance/insulin resistance
The incidence rates of CHD are 2-3 times higher in postmenopausal
women than for those women of the same age who have not yet
undergone menopause. However at present, based on observations
from large scale prospective studies in women, it is still unclear if
the postmenopausal state per se is a risk factor for CVD70.
Another finding that is consistent with the theory that the meno
pausal state per se may not be directly responsible for the increase
in CVD risk is the lack of benefit of hormone replacement therapy
(HRT) in both primary71,72 and secondary prevention trials73,74.
However, menopause before the age of 50, either spontaneous or
surgically induced75, is associated with an increased risk of CVD.
This risk is mainly for CHD and not stroke. This increased risk was
significant even after controlling for age and smoking.
3.3 FAMILY HISTORY OF PREMATURE CHD

A family history of premature CHD is an independent predictor of
CVD risk76. The risk of CHD increases: when the affected individual is a first degree relative
the higher the number of family members with CHD
the younger the age at which family members develop CHD
All first degree relatives of any patient developing CHD before
55 years in men and 65 years in women should have their global
CVD risk assessed and the appropriate prevention strategies
implemented77,78,79.
3.4 DYSLIPIDAEMIA
Lipoprotein levels are similar in prepubertal girls and boys. After
puberty80,
high density lipoprotein cholesterol (HDL-C) levels remain
higher in women compared to men
levels of low density lipoprotein cholesterol (LDL-C) and non
HDL-C levels are lower in young and middle aged women
13
After the menopause80,

total cholesterol (TC) levels increase
LDL-C levels rise and may exceed that of age-matched men
LDL-C particle size shifts towards smaller dense particles
HDL-C levels remain constant
greater postprandial rises in lipoprotein levels after standardized
fat meals
lipoprotein a [Lp(a)] also increases with age
Hormone replacement therapy tends to:
decrease LDL-C
decrease Lp(a)
increase HDL-C
increase triglyceride (TG)
When compared to men:
low HDL-C rather than high LDL-C is more predictive of CVD
risk81,82
high TG is important as a CVD risk factor in older women
especially at levels above 4.5mmol/l11,83,84
TC appears to be associated with CVD only in premenopausal
women or at very high levels (>6.9mmol/l)85
Lp(a) is a determinant of CVD in both premenopausal and post
menopausal women under the age of 66 years83
Women with the metabolic syndrome and/or diabetes tend to have
lower HDL-C, higher TG and a greater proportion of LDL phenotype
B (small dense LDL particles). This atherogenic lipoprotein profile
associated with diabetes is more pronounced in women than
men86.
3.5 HYPERTENSION
In Malaysia, according to the National Health and Morbidity Survey
III (NHMS III 2006), 43% of women above the age of 30 have
hypertension87. In both men and women, blood pressure (BP)
tends to increase with age. Most studies have shown that before
the age of 60, women have lower systolic and diastolic BP than
men88. After the age of 60 years, women have a much steeper rise
in systolic BP88. At the age of 60 years, over 80% of women are
hypertensive89.
Isolated systolic hypertension is more common in older women
than men90. This age related rise in BP, particularly systolic BP
and pulse pressure, contributes substantially to the age-related
increase in CVD and HF in middle aged and elderly women91.
14
Hypertension is more common after the menopause. Postmeno

pausal women are more than twice as likely to have hypertension
as premenopausal women even after adjustment for age and body
mass index (BMI)92.
Hypertension and left ventricular hypertrophy are both stronger
predictors for CVD, HF, CHD and stroke mortality in women than
in men93,94,95.
Hypertension is a leading risk factor for stroke in both men and
women, with a relative risk ratio of 4. For every 7.5mmHg increase
in diastolic BP, the stroke risk increases by 46%96. In the elderly,
systolic BP is a more important CVD risk factor than diastolic BP
and should be the principal target of therapy97. An increase in
systolic BP by 20mmHg is associated with a two fold increase in
the rate of death from stroke, CHD and other vascular causes98.
The cause of hypertension in both men and women is usually
primary. Some causes of secondary hypertension are more
common in women eg fibromuscular renal artery stenosis99.
Women tend to have more labile BP and a higher prevalence of
white coat hypertension than men100. Women are also more likely
to be salt sensitive and have low renin, high volume hypertension
than men101.
Combined oral contraceptive (COC) use may cause a small but
detectable increase in BP102. A small percentage of women develop
frank hypertension. A family history of hypertension, pre-existing
pregnancy-induced hypertension, occult renal disease, obesity,
age >35years and duration of COC use increase susceptibility
to COC-induced hypertension102. This usually resolves within 3
months of the withdrawal of the COC103. Hypertension due to COC
is likely the most frequent cause of secondary hypertension in
young women104.
In contrast, HRT as either oral or transdermal oestrogen alone or in
combination with a progestin, has neutral effects or may lower the
BP in normotensive and in hypertensive women102.
Factors that predispose to pregnancy-induced hypertension also
predispose to CVD in later life. Thus long term follow-up of these
patients is advisable105. (refer section 3.11.3)
15
3.6 DIABETES MELLITUS/PRE-DIABETES

3.6.1 Diabetes mellitus
In Malaysia, the prevalence of diabetes mellitus (DM) in adults age
30 and above has increased from 8.3% in 1996106 (NHMS II) to
14.9% in 200687 (NHMS III). The prevalence of DM increased with
increasing age, from 2.0% in the 18-24 year age group to between
20.8-26.2% among the 50-64 year age group106. There was no
gender difference observed. Type 2 diabetes mellitus (T2DM)
accounts for >95% of the local diabetic population107.
Diabetes mellitus eliminates the female advantage of a lower
CHD prevalence108. Women with diabetes are at increased risk
for all-cause, cardiac and CHD mortality109. The CHD mortality in
diabetic women is 2-5 times that of non-diabetic women110,111. Even
in insulin treated diabetics less than 30 years of age, the CVD
mortality in women is higher than that of diabetic men112.
A meta-analysis of 37 prospective cohort studies, involving 447064
patients found that the overall relative risk of fatal CHD was
significantly greater among women with diabetes (RR:3.50) than
among men with diabetes (RR:2.06)113. The relative risk for fatal
CHD associated with diabetes was 50% higher in women than it
was in men113.
In the last 3 decades, cardiovascular deaths have remained
unchanged for diabetic women while outcomes for non-diabetic
women and men (non-diabetic as well as diabetic) have improved.
This has been shown to be due to disparities in preventive care and
intensity of risk reduction114.
3.6.2 Pre-diabetes
Pre-diabetes includes:
Impaired Fasting Glycemia (IFG)
Impaired Glucose Tolerance (IGT)
Combined IFG and IGT
Table 1: Diagnosis of Pre-Diabetes
Plasma glucose
DM
IFG
Fasting
>7.0
> 6.1 6.9
2hr post-OGTT
>11.1
IGT
>7.8 11.0
16
These dysglycaemic states are also associated with increased

CVD risk and events115,116.
Women with a prior history of gestational diabetes mellitus, a
big baby (birth weight >4kg) or a diagnosis of polycystic ovarian
syndrome are at high risk of developing glucose intolerance/T2DM
and Metabolic Syndrome. They should be screened at regular
intervals for diabetes as well as other CVD risk factors.
3.7 METABOLIC SYNDROME

Metabolic syndrome (Met S) is a constellation of risk factors that
includes the following criteria:
abdominal obesity (waist circumference >80cm/31.5 inches)
elevated fasting TG (>1.7mmol/L)
low HDL-C (<1.29mmol/L)
hypertension (BP >130+/- >85mmHg)
T2DM/IFG/IGT
There are 2 main definitions for the Met S:
International Diabetes Federation (IDF) 2005117
National Cholesterol Education Program Adult Treatment Panel
III (NCEP-ATPIII)118
The difference is that in the IDF definition, abdominal obesity is
the mandatory parameter with presence of 2 other criteria for the
diagnosis, whereas for the NCEP/ATP III, any >3 out of 5 criteria
are adequate.
The presence of Met S predicts the development of CVD and
T2DM.
Unfortunately, the value of Met S as a scientific concept remains
controversial119. The presence of Met S alone does not predict
global CVD risk. Newer risk assessment algorithms119 which include
the above, in addition to the classical CVD risk factors (age, gender,
smoking, LDL-C) are being recommended to better quantify global
CVD risk.
Excess abdominal adipose tissue is associated with insulin
resistance, creating an atherogenic inflammatory milieu,
characterized by high levels of C-reactive protein and other
inflammatory markers (eg, fibrinogen, plasminogen activator
inhibitor-1, cytokines, and adhesion molecules)119,120. Epidemiologic
17
studies have shown a positive correlation between levels of these

biomarkers and CVD risk.
The risk for Met S increases with increasing age. This effect is more
marked in women than men.
Nonalcoholic fatty liver disease (NAFLD) is considered a hepatic
manifestation of the Met S121. Insulin resistance plays a central
role in its pathogenesis. NAFLD has recently emerged as an
independent cardiovascular risk predictor.
3.8 OBESITY
Overweight/obesity increases CVD risk. With increasing body
mass, both CHD mortality and all cause mortality are
increased122,123. Many CVD risk factors (such as dyslipidaemia,
glucose intolerance and hypertension) are associated with
obesity. With increasing degrees of overweight/obesity, there is
an increased likelihood of developing these risk factors.
In Malaysia, between 1996-2006, there has been a marked
increase in the prevalence of obese and overweight males and
females. (see Table 2 and Figure 3A and B)87,124. The prevalence of
overweight/obesity is higher in Malaysian women than men.
Table 2: Prevalence of Overweight/Obesity in NHMS II (1996)
and NHMS III (2006)
Adults
Overweight
BMI 25 29.9
kg/m2
NHMS II
Obese
BMI >30kg/m2
NHMS III NHMS II
Overweight/
Obese
NHMS III NHMS II
NHMS III
Males
15.1%
29.7%
2.9%
10.1%
18.0%
39.8%
Females
17.9%
28.6%
5.7%
17.3%
23.6%
45.9%
Overall
16.6%
29.1%
4.4%
14.0%
21.0%
43.1%
18
The prevalence shown above uses the international definition

of overweight/obesity. This is to allow comparison between
the NHMS II and NHMS III. The Asia Pacific definition125 for
overweight/obesity uses different cutoff points i.e. overweight
>23 to <25kgm2; obese >25kgm2. The reason for this lower cut
off points is because Asians have a higher CVD risk at lower
BMI126,127. Furthermore, Asians also have a higher abdominal
adiposity compared to Caucasians for the same BMI128.
Figure 3A: Prevalence of Obesity
according to Gender in NHMS II (1996) vs NHMS III (2006)
Figure 3B: Prevalence of Overweight according to Gender in

NHMS II (1996) vs NHMS III (2006)
19
With increasing age, there is an increased prevalence of

overweight and obese individuals especially in females. For any
given BMI, women have more total body fat. After the menopause,
women have an increase in abdominal visceral fat deposition.
Waist circumference correlates better with abdominal fat content
than BMI. Gender specific waist circumference cutoff points for
CVD risk have been established. In Asians, a waist circumference
of >80 cm in women and >90cm in men raises CVD risk117.
Weight gain during adulthood is associated with a significantly
increased risk of CHD, independent of physical activity level129. In
a large prospective study in women, those who gained substantial
weight after age 18 were at significantly increased risk of CHD,
T2DM and total mortality compared with women who remained
within 5lbs (2.3kg) of weight at age 18130. For each increase in body
weight of approximately 1kg, the risk of CHD mortality increases
by 1-1.5%131.
Although obesity is associated with CHD risk and weight loss has
been shown to be beneficial, weight cycling (repeated weight loss
and weight gain) increases CHD mortality132,133. For benefits of
weight loss, refer table 3.
Table 3: Beneficial effects of a 10% weight loss in the obese
individual134
Mortality
Blood
Pressure
Diabetes
Lipids
>20% total
>30% diabetes related
>40% obesity related cancer
10mmHg systolic
20mmHg diastolic
30-50% in fasting glucose
50% in developing diabetes
15% in HBA1c
10% total cholesterol
15% LDL-cholesterol
30% triglycerides
8% HDL-cholesterol
The above are seen in addition to psychological, physical and other

metabolic benefits.
20
3.9 SMOKING
Smoking is a very important cardiac risk factor in both men and

women. This risk is dose related. In women, even with minimal use,
CVD risk is elevated (RR: 2.4 for 1.4 cigarettes/day)81,135. The risks
associated with smoking are consistently higher in women than
in men and are not age dependent136. Cigarettes can induce an
unfavourable lipid profile, increase inflammation, thrombosis and
oxidative stress. As a result women, especially premenopausal
women, lose their natural protection against atherosclerotic
vascular disease.
In Malaysia, only 4.4% of women smoke and these are mainly
those under the age of 3087.
Young women who smoke and use COC have a very high CVD
risk. They have more than 5-fold increase in the risk of MI when
compared to COC users who do not smoke137,138. Women smokers
above the age of 34 years who use COC are at especially high
risk139.
Women switching to low yield cigarettes with reduced tar, nicotine,
and carbon monoxide have the same CVD risk as those who smoke
higher-yield brands140.
3.10 PHYSICAL ACTIVITY

Epidemiological studies have shown that low physical activity is
a strong and independent risk factor for both CVD and all-cause
mortality141,142.
Physical activity includes:
Leisure-time physical activity defined as:
high: participation in recreational sports (eg, running, jogging,
gymnastics, swimming or heavy gardening) or in intense
training or sports competitions for at least three hours a
week
moderate: walking, cycling or practicing some other form of
light exercise (gardening) at least four hours per week
low: reading, watching TV or working in the household
without much physical activity
Occupational physical activity defined as:
high: lots of walking and lifting at work, taking the stairs or
walking uphill (eg, industrial work and farm work)
moderate: walking quite a lot at work without lifting or carrying
heavy objects (eg, store assistant, light industrial worker)
21
low: mostly sedentary work without much walking (eg,

secretary, working in an office)
Commuting activity defined as:
high: more than 30 min physical exercise (walking, cycling)
every day while getting to work and back home
moderate: exercising (walking, cycling) between 15 and 30
min daily on the way to work and back home
low: exercising less than 15min daily on the way to work and
back home (motorized transport, no walking or cycling)
Moderate and high levels of leisure time and/or occupational
physical activity or high levels of commuting activity in women are
associated with a reduced CVD and all-cause mortality143 and 10
year risk of CHD144.
However even light-to-moderate activity is associated with lower
cardiac risk in women. Walking for at least 1 hour per week
predicted lower CHD risk. Time spent walking was more important
than walking pace144. These benefits of physical activity were seen
in all women irrespective of the baseline CHD risk144,145.
Obesity is often associated with physical inactivity and both
independently contribute to the development of CHD in women.
Being physically active attenuates moderately but does not
eliminate the adverse effects of obesity on cardiac risk. Being
lean does not counteract the increased risk of CHD associated
with physical inactivity. The lowest risk of CHD is observed among
physically active, lean women129.
When compared to women who had a BMI of 18.5 to 24.9kg/m2
and were physically active (exercise >3.5hours/week), the RR of
CHD were:
3.44 for women who were obese (BMI >30kg/m2) and sedentary
(exercise <1hour/week)
2.48 for women who were active but obese
1.48 for women who had a healthy weight but were
sedentary129
A BMI of greater than 25kg/m2 and less than 3.5 hours of exercise
per week accounts for 59% deaths due to CVD146.
22
Women who are physically active tend to have a more favourable

CVD risk profile. Physical fitness is independently associated with
lower TG, higher HDL-C, lower TC/HDL-C ratio, lower BP and
lower cigarette smoking147,148.
3.11 OTHERS
3.11.1 Oral Contraceptives
Current use of low dose COC (<50g of estrogen) increases the
risk of CVD. In a recent meta-analysis, the risk of MI was increased
by 1.84 and ischaemic strokes by 2.1244. However, third-generation
COCs appear to be safer with an increased risk of ischaemic
stroke but not MI44.
The increased risk of CVD among COC users could be due to their
effect on:
Increasing BP
Inducing glucose intolerance
Unfavorable effects on lipids Higher TG and TC levels149
Procoagulant effects150
Newer COCs have fewer metabolic side effects151.
Current or prior use of low dose COC is not associated with a
greatly increased risk of MI in healthy non smokers. However
women who smoke heavily are at high risk of MI152. This risk was
independent of the type of formulation or dose of estrogen used.
3.11.2 Hormone replacement therapy
Combined hormone therapy of progestin and oestrogen for
postmenopausal women increases the risk of CHD and stroke71.
In the first year of treatment, HRT was associated with a significant
increase in the risk of nonfatal MI or coronary death and an
approximate 3-fold increase in the risk of venous thromboembolic
events73.
For 10,000 women treated with a estrogen/progestin combination
for a year, there were 5 fewer hip fractures and 7 more CHD
events, 8 more strokes, 8 more pulmonary emboli and 8 more
invasive breast cancers71. The oestrogen only arm in women with
prior hysterectomy in the Womens Health Initiative study found no
increase in CHD and breast cancer risk but an increase in the risk
of stroke and pulmonary embolism153.
23
Therefore, HRT is not recommended either for primary or secon

dary prevention of CVD71,72,73,74,153. It should be reserved for women
with moderate to severe vasomotor symptoms and preferably
limited to less than 4 years.
The role of selective estrogen receptor modulators in CVD
prevention is still being addressed in ongoing trials.
3.11.3 Pre-eclampsia
Following pre-eclampsia, women are at an increased risk of CVD105.
The RR for the following are increased:
hypertension by 3.70
CHD by 2.16
stroke by 1.81
venous thromboembolism by 1.79
overall mortality by 1.49
It is not known if this association is due to a common cause for
pre-eclampsia and CVD, an effect of pre-eclampsia on disease
development, or both.
3.11.4 Alcohol
Low levels of alcohol intake has been found to reduce all cause
mortality in both men and women. In women this should not exceed
1-2 drinks per day154,155. At moderate to high levels, the risk of death
is higher in women than in men, probably owing to increasing
risk of cancer156. Heavy consumption of alcohol is also related to
hypertriglyceridemia, uncontrolled hypertension, congestive heart
failure and liver disease.
When men and women consume the same amount of alcohol,
women experience higher blood alcohol concentrations. This is
because women metabolize ethanol differently and have a lower
gastric alcohol dehydrogenase activity, resulting in higher blood
ethanol levels.
Pregnant women are advised to refrain from alcohol consumption.
Alcohol intake should not exceed 14 units per week in women (see
appendix 1).
24
Key Messages:
Important cardiovascular risk factors in women include:
personal history of CHD and/or CHD equivalents
These women are at high risk for a recurrent vascular
event. Intensive preventive strategies should be
implemented
age (over 55)
family history of premature CHD
All women with a family history of CHD should have their
CVD risk assessed.
dyslipidaemia
hypertension
Post menopausal women are increasingly likely to become
hypertensive.
Even slightly elevated BP poses a risk in the long term
and should be addressed.
diabetes mellitus/pre-diabetes
metabolic syndrome
obesity
smoking
physical inactivity
25
4. TOTAL CARDIOVASCULAR RISK ASSESSMENT

All asymptomatic apparently healthy women should have their
cardiovascular risk assessed. The CVD risk factors should be
identified and appropriately managed to target. This should be an
integral component of periodic health examinations of all women in
addition to their regular gynaecological and breast examinations.
Cardiovascular risk refers to the likelihood of a woman developing
a cardiovascular event, fatal or non fatal, over a defined period of
time. Determining an individuals CVD risk would help:
identify high risk women
guide the intensity of preventive strategies. Women at high
risk should undergo intensive lifestyle interventions and where
appropriate, drug therapies
improve physician recognition, detection and treatment of risk
factors
There are several validated multivariate risk models that can
be used to assess CVD risk in asymptomatic individuals. These
models are based on multifactorial risk analysis in populations that
have been followed for several years. These include the:
Framingham Risk Score (FRS) modified by The National
Cholesterol Education Program Expert Panel on Detection,
Evaluation and Treatment of High Blood Cholesterol in
Adults (Adult Treatment Panel III)65 - This assesses the risk of
developing CHD (cardiac death, MI) only.
The newer risk models assess total CVD risk instead of CHD
risk alone.
Framingham Risk Score (FRS) - A more recent modification of
this score assesses the risk of developing CVD157. It provides
sex specific CVD risk scores and allows for the calculation of an
individuals heart age. (Appendix 2)
SCORE system developed by the European Society of
Cardiology66. This system predicts the occurrence of a first fatal
CVD event and allows the estimation of total CVD risk projected
to age 60.
WHO/ISH Cardiovascular Risk Prediction Charts 67
QRISK (risk score using the QRESEARCH database) is a CVD
risk prediction algorithm formulated in the United Kingdom
(UK)158
ASSIGN ( ASsessing cardiovascular risk using SIGN guidelines)
based on a UK population159
26
The FRS has been validated in white and black American men and
women but may not be that predictive in other populations160,161.
It also has its limitations in women162 because it focuses on short
term (10 year) risk of MI and CHD mortality. Although women have
a low absolute risk of CVD, due to their longer life expectancy, the
average lifetime risk in women is substantial (approaching 1 in 2)163.
For this reason, the risk stratification in Table 4 is recommended.
This model does not include newer risk factors such as hs-CRP.
In addition, it does not include the following risk factors that have
been shown to increase CVD risk in asymptomatic individuals:
left ventricular hypertrophy in hypertensives This can be
detected either by ECG or echocardiography
ABI detected by doppler ultrasound
carotid intima-media thickness detected by ultrasound
coronary calcifications indicating subclinical vascular disease detected by CT
These risk factors may provide incremental information to traditional
risk factor assessment in certain asymptomatic individuals at
intermediate CVD risk. Their presence would elevate the individual
to a higher CVD risk, indicating the need for more aggressive
preventive strategies. However at present, routine screening for
these risk factors is not recommended164.
27
Table 4: Classification of CVD Risk In Women*

High Risk
Established CHD and/or CHD Equivalents

which are :
- Cerebrovascular disease
- PAD
- Abdominal aortic aneurysm
- Diabetes mellitus
- Endstage or chronic kidney disease
- Multiple risk factors that confer a 10 year
(FRS) of >20% or a SCORE risk of >5%
At Risk
>1 major risk factor for CVD including:

- Family history of premature CVD (CVD at
age <55 years in male relative and <65 years
in female relative)
- Dyslipidaemia
- Hypertension
- Cigarette smoking
- Physical inactivity
- Obesity especially central obesity
- Metabolic syndrome
Optimal Risk
FRS <10% and a healthy lifestyle with no risk

factors
* Adapted from the Evidence Based Guidelines for Cardiovascular Disease

Prevention In Women: 2007 Update. Circulation 2007; 115 : 1481-1501.
From an early age, all women should know their levels and
significance of their risk factors. All women above the age of 40
years should know their global CVD risk. (refer Table 4)
History: Looking for symptoms of CHD or CHD Equivalents,
Family history of premature CHD, smoking status, physical
activity
Women with established CVD (CHD and CHD Equivalents) are
at High Risk of a future vascular event. They have a risk of a
28
recurrence of their angina or the occurrence of death that is 1.5

to 15 times that of the general population165. These high risk
women should have the most intensive lifestyle intervention and
appropriate drug therapies.
Women At Risk should have their global risk for CVD reduced by
lifestyle modification and drug treatment, where appropriate. If CVD
is suspected, they should undergo the relevant diagnostic tests and
treatment.
Women at Optimal Risk should be encouraged to continue their
healthy lifestyle and to maintain their ideal weight.
Key messages:
All women above the age of 40 years should know their CVD
risk.
History: Looking for symptoms of CHD or CHD
Equivalents, family history of premature CHD, smoking
status, physical activity
Prevention of CVD involves:
High Risk: Intensive risk factor reduction with lifestyle
and pharmacological measures to achieve target levels.
At Risk: non pharmacological intervention with diet and
physical activity. If targets not achieved, pharmacological
therapy is indicated.
Optimal risk: Continue with healthy lifestyle measures
29
5. RECOMMENDATIONS FOR PREVENTION OF CVD IN

WOMEN
The INTERHEART study found that 9 potentially modifiable
factors accounted for over 90% of the population attributable
risk of a first MI166. These included dyslipidaemia, hypertension,
diabetes, smoking, abdominal obesity, psychosocial factors,
regular physical exercise, daily consumption of fruits and
vegetables and regular alcohol consumption163. The effects of
these risk factors were similar in both men and women across
different geographic regions and ethnicity. It was estimated that
90% of CHD events occurred in people with at least 1 elevated
risk factor167.
Borderline risk factors contribute incrementally to this CVD risk167.
Thus it is important to assess the global CVD risk since mildly
raised levels of several risk factors in the long term, will result in
increased total CVD risk.
Prevention should be aimed at a reduction in global CVD risk
rather than treating individual risk factors alone. All CVD risk
factors should be identified and managed aggressively according
to guidelines.
5.1 GENERAL RECOMMENDATIONS

The following healthy lifestyle measures are important in all
women. By adopting a healthy lifestyle, women can reduce their
CVD risk by as much as 55166 to 82%168.
5.1.1 Nutrition
Level I, Healthy food choices that reduce CVD risk should be encouraged168- Grade I,
Grade A 175
Level A
Level III, General recommendations should fit in with the local culture. Grade I,
Level C
Grade C Energy intake should be adjusted to avoid overweight/obesity.
Encourage:
fruits
vegetables
whole grain cereals and bread
fish especially oily (such as ikan tenggiri, carp)
lean meat
low fat milk and cheese
30
Grade I, Replace saturated fat with monounsaturated and polyunsatu- Level I,

Level B rated fats from vegetable and flower and to reduce total fat <30% Grade A
of energy, of which <1/3 is saturated176,177.
Nutritional recommendations should be individualized depending

on risk factors dyslipidaemia, hypertension, diabetes and
obesity.
Grade I, Some hypertensive patients (especially the elderly) are sensitive Level I,
Level A to salt. In general, reduce daily salt intake to approximately 1- 1 Grade A
tsp salt178,179. This can be achieved by reducing salt in cooking

and by not adding table salt or soy sauce. Choose fresh or frozen
unsalted foods as processed food is generally high in salt.
Grade IIa, In women with CHD, omega-3-fatty-acid

Level B found to be beneficial173,175.
(>1gm/day) has been Level I,
Grade B
5.1.2 Physical activity

Grade I, Women should be encouraged to exercise for at least 30 minutes Level II-1,
Level B on most days of the week129, 141,142, 145,180. Women who need to lose Grade B
weight or sustain weight loss should exercise more.
Even small increases in physical activity is beneficial (eg. walking
1 hour per week or using stairs instead of the lift or escalator)145.
5.1.3 Weight maintenance/reduction
Grade I, Ideal BMI for Asian women is 18.5 - <23kg/m
Level B circumference is <80cm (31.5 inches)117,125.
and ideal waist Level II-2,

Grade B
Weight control can be achieved by restriction of total calorie intake

and regular physical activity.
5.1.4 Cigarette smoking
should not smoke and should avoid environmental Level II-2,
Grade B
smoke181.
Grade I, Women
Level B tobacco
5.1.5 Aspirin
Grade I, Aspirin is indicated for secondary prevention
Level A CHD and CHD risk equivalents182,183.
Grade I, For primary
Level B years184.
31
in all women with Level I,
Grade A
prevention, aspirin is only beneficial in women >65 Level I,
Grade A
5.2 TREATMENT OF SPECIFIC RISK FACTORS

Aggressive risk factor reduction should be instituted in all High
Risk patients.
5.2.1 Dyslipidaemia
The primary target of therapy is LDL-C.
In women especially in diabetics, low HDL-C and high TG are
also important risk factors and are the secondary targets of
therapy185.
5.2.1.1 Targets of therapy
Table 5: Targets of Therapy in Dyslipidaemia
High Risk
At Risk
Optimal Risk
LDL-C
<2.6mmol/l with
an option of
<2.0mmol/l
<3.4mmol/l
<4.1mmol/l
HDL-C
>1.0mmol/l
TG
<1.7mmol/l
<2.3mmol/l
<2.3mmol/l
5.2.1.2 Management of Dyslipidaemia: Primary Prevention

Level III, The cornerstone of management of women At Risk and Optimal Grade I,
Grade C Risk is lifestyle modification with advice on a healthy diet and Level C
physical activity.
Level III, Women At Risk

Grade C considered for
who do not achieve their target levels should be Grade I,

pharmacological intervention although there is Level C
little data on the effect of lipid lowering therapy on CHD events
for primary prevention in women. Current practice is to treat At
Risk women in the same manner as men based on extrapolation
of benefit in men at similar risk.
Women with genetic dyslipidaemias such as familial
hypercholesterolemia with very high levels of TC or LDL-C may
be considered for lipid lowering therapy from the outset.
32
5.2.1.3 Management of Dyslipidaemia: Secondary Prevention

Grade I, Numerous studies on secondary prevention have shown that Level I,
Level A women have similar benefits on CVD outcomes as men186-189.
Grade A
These High Risk women should have early drug therapy. Statins
should be the drug of first choice186-188.
Grade I, Statins should not be used in
Level C become pregnant or who are
women who are pregnant, intend to Level III,

Grade C
breast feeding.
Grade IIa, In patients who have normal LDL-C but have a

Level B high TG, fibric acid derivatives may be used189.
low HDL-C and Level I,
Grade A
The management of dyslipidaemia in women is as in the

Malaysian Clinical Practice Guidelines on Dyslipidaemia, 2003185.
(see Appendix 3)
5.2.2 Hypertension
5.2.2.1 Targets of Therapy
target BP in most patients should be <140/85mmHg190.
Grade I,
Level A The
Level I,
Grade A
The guidelines recognize that the risk of target organ damage

extends to BP below this level and the true threshold for CVD
risk should be flexible and dependent on the total risk of the
individual.
Grade I, In patients
Level A the target
with CHD, diabetes mellitus or chronic kidney disease Level I,

BP should be <130/80mmHg. In the presence of Grade A
proteinuria of >1g/24hr, target BP should be <125/75mmHg190.
(see Appendix 4A & 4B)
For recommended pharmacotherapy refer Appendix 4C.
5.2.2.2 Gender Specific issues

Current guidelines for the treatment of hypertension are not
gender specific. There are however some gender differences.
Women are:
less likely than men to have BP controlled with lifestyle
interventions alone191
less successful in losing weight191
more sensitive and more likely to respond to salt restriction192
more likely to develop hyponatraemia and/or hypokalaemia
associated with diuretic therapy193
33
less likely to respond to -blockers191

more likely to develop pedal oedema with calcium channel
blockers
twice as likely as men to develop ACEI induced cough194
Special issues in women
pre conception counseling is important in young women with
hypertension
women in the reproductive age should preferably avoid ACEI
and angiotensin receptor blockers
in pregnancy, the drugs of choice are methyldopa, nifedipine
and labetolol
young women with high CVD risk especially after the age of 35
should avoid the use of COC. If necessary, progesterone only
contraceptive may be considered
HRT-related change in BP is likely to be modest and should not
preclude its use in normotensive or hypertensive women
5.2.3 Diabetes
5.2.3.1 Targets of therapy
Table 6: Targets of Therapy In Diabetes
Unit
HbA1c
Plasma
glucose
Grade,
Level
Level,
Grade
I, A
I, A
<130/80 mmHg
I, A
I, A
<2.6mmol/L
With an option of
<2.0mmol/L
I, A
I, A
IIa, B
I, A
<6.5%
Fasting
<6.1mmol/L
2hr PP
<7.8mmol/L
BP
LDL-C
Lipids
Target
TG
<1.7mmol/L
HDL-C
>1.0mmol/L
Refer Malaysian CPG for management of Type 2DM (2004). Specific

local guidelines for the management of diabetic complications
(CPGs on Diabetes Nephropathy 2006, Diabetes Retinopathy and
Diabetic Foot 2004) are also available.
34
5.2.4 Overweight and Obesity

Treatment of overweight and obesity can be achieved through a
variety of modalities which include:
changes in dietary composition
low-calorie diet (LCD)
very low-calorie diet (VLCD)
physical activity
behavior therapy
drug therapy
surgery
Certain weight loss therapies may be inappropriate in the
following circumstances:
illnesses that might be exacerbated by caloric restriction
serious, acute psychiatric illness
pregnancy or lactation
5.2.4.1 Overall Goals for Weight Loss Management
10% loss of the initial body weight is associated with Level III,
Grade C
significant health benefits (see Table 3)134
Overweight/obese women who lose weight intentionally over a
year, have been shown to have significantly reduced mortality
rates195
Maintain lower weight over the long-term. It is better to
maintain a moderate loss over the long-term than it is to
achieve a greater weight loss that cannot be maintained
Prevent weight regain
Grade IIa,
Level B
5.2.5 Others
The following has been shown to prevent strokes:
Anticoagulation with warfarin in nonvalvular atrial fibrillation if
the following are present:
heart failure, impaired left ventricular function, hyper Level I,
Grade I,
Level A
tension, age over 75 years, diabetes and previous history Grade A
of stroke or TIA196
age between 64 to 75 years, female gender and coronary Level I,
Grade I,
Level B
Grade A
artery disease194
The risk of bleeding and patient preferences must however be
taken into consideration before initiating therapy.
35
Level I,
Grade B
Anticoagulation with warfarin is not indicated for the Grade I,

prevention of thromboembolism in women with lone atrial Level B
fibrillation who do not have heart disease and who are below
the age of 60 years196.
The following have been shown not to be useful/effective and may

be harmful for CVD in women:
Grade III,
Level I, Anti oxidants197,198
Level A
Grade A
Level I,
Grade A
Hormone Replacement Therapy71,72,73,64,153
Grade III,
Level A
36
REFERENCES
1. Number of discharges and deaths in government hospitals. Information and
Documentation System Unit. Ministry of Health, Putrajaya 2008. (Dr. Feisul Idzwan
Mustapha NCD, personal communication)
2. Vaccarino V, Parsons L, Every NR et al. Sex based differences in early mortality
after myocardial infarction. National Registry of Myocardial Infarction 2 participants.
N Engl J Med 1999; 341 : 217-25.
3. Becker RC, Terrin M, Ross et al. Comparison of clinical outcomes for women and
men after acute myocardial infarction. Ann Intern Med 1994; 120 : 635-45.
4. Moen EK, Miller DP, Asher CR et al. Long term follow-up of gender specific
outcomes after thrombolytic therapy for acute myocardial infarction from the
GUSTO-1 Trial. J Womens Health 1997; 6 : 285-93.
5.
Cupples LA, D Agostino RB. Some risk factors related to the annual incidence of
cardiovascular disease and death using pooled repeated biennial measurements:
Framingham Heart Study, 30 year follow-up. In: Kannel WB, Wolf PA, Garrison
RJ eds. The Framingham Heart Study: an epidemiological investigation of heart
disease. Rockville, MD : National Heart, Lung and Blood Institute; 1987. NIH
Publications 87-2703,Section 34.
6.
Bonita R. Epidemiology of stroke. Lancet. 1992; 339 : 342344
7.
American Heart Association. Heart Disease and Stroke Statistics2004 Update.

Dallas, Tex: American Heart Association; 2003.
8.
Murray CJL, Lopez AD. Mortality by cause for eight regions of the world: Global
Burden of Disease Study. Lancet. 1997; 349 : 12691276.
9.
Prencipe M, Ferretti C, Casini AR, Santini M, Giubilei F, Culasso F. Stroke, disability,

and dementia: results of a population survey. Stroke. 1997; 28 : 531536.
10. Skoog I, Nillson L, Palmeretz B, Andreasson LA, Svanborg A. A population-based

study of dementia in 85-year-olds. N Engl J Med 1993; 328 : 153158
11. Douglas PS, Ginsburg GS. The evaluation of chest pain in women. N Engl J Med
1996; 334 : 1311-5
12. Lerner DJ. Kannel WB. Patterns of coronary heart disease morbidity and mortality
in the sexes: a 26 year follow up of the Framingham population. Am Heart J 1986;
111 : 383-90
13. Milner KA, Funk M, Arnold A, Vaccarino V. Typical symptoms are predictive of acute
coronary symptoms in women. Am Heart J 2002; 143 : 283-8
14. Shaw LJ, Bairey Merz CN, et al. Insights from the NHLBI-sponsored Womens
Ischaemia Syndrome Evaluation (WISE) study. J Am Coll Cardiol 2006; 47 : 4S20S
15. Kwok Y, Kim G, Grady D et al. Meta analysis of exercise testing to detect coronary
disease in women. Am J Cardiol 1999; 83 : 660 -6.
16. Mora S, Redberg RF, Cui Y et al. Ability of Exercise Testing to Predict Cardiovascular
and All-Cause Death in Asymptomatic Women. 20-Year Follow-up of the Lipid
Research Clinics Prevalence Study. JAMA2003; 290 : 1600-1607.
17. Mieres JH, Shaw LJ, Hendel RC et al. Am Society of Nuclear Cardiology: task force
on women and coronary artery disease. J Nuc Cardiol 2003; 10 : 95-101.
18. Anderson JL, Adams CD, Antman EM et al ACC/AHA 2007 Guidelines for the
Management of Patients With Unstable Angina/Non ST-Elevation Myocardial
Infarction Executive Summary: A Report of the American College of Cardiology/
American Heart Association Task Force on Practice Guidelines (Writing Committee
to Revise the 2002 Guidelines for the Management of Patients With Unstable
Angina/Non ST-Elevation Myocardial Infarction) Developed in Collaboration with
37
the American College of Emergency Physicians, the Society for Cardiovascular

Angiography and Interventions, and the Society of Thoracic Surgeons Endorsed
by the American Association of Cardiovascular and Pulmonary Rehabilitation and
the Society for Academic Emergency Medicine J Am Coll Cardiol 2007; 50: 652 726.
19. Kaski JC, Rosano GM, Collins P et al. Cardiac syndrome X: clinical characteristics
and left ventricular function. Long-term follow-up study. J Am Coll Cardiol 1995; 25
: 807-814.
20. Reis SE, Holubkov R, Conrad Smith AJ, et al. Coronary microvascular dysfunction
is highly prevalent in women with chest pain in the absence of coronary artery
disease: results from the NHLBI WISE study. Am Heart J 2001; 141 : 735-741.
21. Buchthal SD, den Hollander JA, Merz CN, et al. Abnormal myocardial phosphorus-31
nuclear magnetic resonance spectroscopy in women with chest pain but normal
coronary angiograms. N Engl J Med 2000; 342 : 829-835.
22. Chauhan A, Mullins PA, Thuraisingham SI, et al Abnormal cardiac pain perception
in syndrome X. J Am Coll Cardiol 1994; 24 : 329-335.
23. Cannon RO 3rd, Quyyumi AA, Schenke WH, et al. Abnormal cardiac sensitivity in
patients with chest pain and normal coronary arteries. J Am Coll Cardiol 1990; 16
:1359-1366.
24. Pasceri V, Lanza GA, Buffon A et al A. Role of abnormal pain sensitivity and
behavioral factors in determining chest pain in syndrome X. J Am Coll Cardiol
1998; 31 : 62-66.
25. Bugiardini R, Manfrini O, Pizzi C, Fontana F, Morgagni G. Endothelial function
predicts future development of coronary artery disease: a study of women with
chest pain and normal coronary angiograms. Circulation 2004; 109 : 2518-2523.
26. Cannon RO, 3rd, Brush JE, Jr., Schenke WH, Tracy CM, Epstein SE. Beneficial
and detrimental effects of lidoflazine in microvascular angina. Am J Cardiol. 1990;
66 : 37-41.
27. Kemp HG, Kronmal RA, Vlietstra RE, Frye RL. Seven year survival of patients with
normal or near normal coronary arteriograms: a CASS registry study. J Am Coll
Cardio. 1986; 7 : 479-483.
28. Kannel WB, Wilson PWF, DAgostino RB, Cobb J. Sudden coronary death in
women. Am Heart J 1998; 136 : 205212
29. Cupples LA, Gagnon DR, Kannel WB. Long and short term risk of sudden coronary
death. Circulation 1992; 85 : I11I18
30. Holmberg M, Holmberg S, Herlitz J, Gardelov B. Survival after cardiac arrest
outside hospital in Sweden. Resuscitation 1998; 36 : 2936
31. Lerner DJ, Kannel WB. Patterns of coronary heart disease morbidity and mortality
in the sexes: A 26-year follow-up of the Framingham population. Am Heart J 1986;
111 : 383390
32. Buxton A, Hafley G, Lehmann M, et al. Prediction of sustained ventricular
tachycardia inducible by programmed stimulation in patients with coronary artery
disease. Circulation 1999; 99 : 18431850
33. Vaitkus P, Kindwall K, Miller J et al Influence of gender on inducibility of ventricular
arrhythmias in survivors of cardiac arrest with coronary artery disease. Am J
Cardiol 1991; 67 : 537539
34. Aronson D, Burger A. The effect of sex on ventricular arrhythmic events in patients
with congestive heart failure. Pacing Clin Electrophysiol 2002; 25 : 2061211
35. DG Wyse, A Hallstrom, R McBride, JD Cohen et al Events in the Cardiac Arrhythmia
Suppression Trial (CAST): mortality in patients surviving open label titration but not
randomized to double-blind therapy. J Am Coll Cardiol 1991; 18 : 20-28
38
36. V R. R. Makkar, B. S. Fromm, R. T. Steinman et al Female gender as a risk factor

for torsades de pointes associated with cardiovascular drugs. JAMA. 1993; 270 :
2590-2597
37. Kitzman DW, Gardin JM, Gottdiener JS, et al., for the Cardiovascular Health Study
Research Group. Importance of heart failure with preserved systolic function in
patients> o r = 65 years of age. CHS Research Group. Cardiovascular Health
Study. Am J Cardiol. 2001; 87 : 413419.
38. Vasan RS, Larson MG, Benjamin EJ, et al. Congestive heart failure in subjects with
normal versus reduced left ventricular ejection fraction: prevalence and mortality in
a population-based cohort. J Am Coll Cardiol 1999; 33 : 19481955.
39. Stramba-Badiale M, Fox KM, Priori SG et al. Cardiovascular diseases in women:
a statement from the policy conference of the European Society of Cardiology. Eur
Heart J2006; 27: 994-1005.
40. Kannel W, Sorlie P, McNamara P. Prognosis after initial myocardial infarction: The
Framingham Study. Am J Cardiol. 1979 ; 44 : 53-59
41. Adams K, Dunlap S, Sueta C, et al. Relation between gender, aetiology and
survival in patients with symptomatic heart failure. J Am Coll Cardiol 1996; 28 :
1781-1788.
42. Towfighi A, Saver JL, Engelhardt R et al. A midlife stroke surge among women in
the United States. Neurology 2007; 69: 1898 - 1904.
43. Collaborative Group for the study of stroke in young women. Oral contraceptives
and stroke in young women. Associated risk factors. JAMA 1975; 231 : 718-22.
44. Baillargeon J-P, McClish DK, Paulina A. Essah PA et al. Association between the
Current Use of Low-Dose Oral Contraceptives and Cardiovascular Arterial Disease:
A Meta-Analysis. J Clin Endo & Metabolism 2005; 90 : 3863-3870.
45. Viscoli CM, Brass LM, Kernan WN et al. A clinical trial of estrogen-replacement
therapy after ischaemic stroke. N Engl J Med 2001; 345: 12431249.
46. Marie-Germaine Bousser, MD Stroke in Women. The 1997 Paul Dudley White
International Lecture. Circulation 1999; 99 : 463-467.
47. Etminan M, Takkouche B, Isorna FC, Samii A. Risk of ischaemic stroke in people
with migraine: systematic review and meta-analysis of observational studies. Br
Med J2005; 330 : 63-64.
48. MacClellan LR, Giles W, Cole J et al. Probable Migraine With Visual Aura and Risk
of Ischaemic Stroke. The Stroke Prevention in Young Women Study. Stroke 2007;
38 : 2438 -45.
49. Higgins JP, Higgins JA. Epidemiology of Peripheral arterial disease in women. J.
Epidemiol 2003; 13 :1-14
50. Diehm C, Lange S, Darius H et al. for the getABI (German epidemiological study
on ankle brachial index )Study Group. Association of low ankle brachial index with
high mortality in primary care Eur Heart J 2006; 27 : 17431749.
51. Lamina C, Meisinger C, Heid IM et al for the KORA Study Group. Association
of ankle-brachial index and plaques in the carotid and femoral arteries with
cardiovascular events and total mortality in a population-based study with 13 years
of follow-up. Eur Heart J 2006; 27 : 25802587
52. Norgren L, Hiatt WR, Dormandy JA et al on behalf of the TASC II Working Group.
Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC
II) ;J Vasc Surg 2007; 45 :(Suppl) : S 5-67.
53. Hirsch AT, Haskal ZF, Hertzer NR et al for the Writing Committee to Develop
Guidelines for the Management of Patients With Peripheral Arterial Disease. ACC/
AHA Guidelines for the Management of Patients With Peripheral Arterial Disease
(Lower Extremity, Renal, Mesenteric, and Abdominal Aortic): Executive summary
a collaborative report from the American Association for Vascular Surgery/Society
for Vascular Surgery, Society for Cardiovascular Angiography and Interverntions,
39
Society for Vascular Medicine and Biology, Society of Interventional Raidology,

and the ACC/AHA Task Force on Practice Guidelines (Writing Committee to
Develop Guidelines for the Management of Patients With Peripheral Arterial
Disease) endorsed by the American Association of Cardiovascular and Pulmonary
Rehabilitation; National Heart, Lung, and Blood Institute; Society for Vascular
Nursing; TransAtlantic Inter-Society Consensus; and Vascular Disease Foundation.
J Am Coll Cardiol 2006; 47 :1239-312.
54. Stewart K,Hiatt W, Regensteiner J, Hirsh A. Exercise training for claudication. N
Engl J Med 2002; 347 : 1941-51.
55. Regensteiner J,Ware JJ, McCarthy W et al. Effect of cilostazol on treadmill walking,
community- based walking ability, and health related quality of life in patients with
intermittent claudication due to peripheral arterial disease: meta analysis of 6
randomized controlled trials. J Am Geriatr Soc 2002; 50 : 1939-46.
56. Mondillo S, Ballo P, Barbati R et al. Effects of simvastatin on walking performance
and symptoms of intermittent claudication in hypercholesterolemic patients with
peripheral vascular disease. Am J Med 2003; 114 : 359-64.
57. Mohler III E, Hiatt W,Creager M. Cholesterol reduction with atorvastatin improves
walking distance in patients with peripheral arterial disease. Circulation 2003; 108;
1481-6.
58. CAPRIE Steering Committee. A randomized, blinded, trial of clopidogrel versus
aspirin in patients at risk of ischaemic events (CAPRIE). Lancet 1996; 348 :
13291339
59. The Scandinavian Simvastatin Survival Study Group. Randomized trial of
cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian
Simvastatin Survival Study (4S). Lancet 1994; 344 : 1383-1389
60. Yusuf S, Sleight P, Pogue J et al. Effects of an angiotensin-converting-enzyme
inhibitor, ramipril, on cardiovascular events in high-risk patients. The Heart
Outcomes Prevention Evaluation Study Investigators. N Engl J Med 2000; 342
:145-53.
61. Radack K, Deck C. Beta-adrenergic blocker therapy does not worsen intermittent
claudication in subjects with peripheral arterial disease. A meta-analysis of
randomized controlled trials. Arch Intern Med 1991; 151 :1769-76.
62. Miyajima R, Sano K, Yoshida H. Beta-adrenergic blocking agents and intermittent
claudication: systematic review.Yakugaku Zasshi 2004; 124 :825-31.
63. Jaffer FA; ODonnell CJ; Larson MG et al. Age and Sex Distribution of Subclinical
Aortic Atherosclerosis. A Magnetic Resonance Imaging Examination of the
Framingham Heart Study Arterioscl Thromb Vasc Bio. 2002 ; 22 : 849-54.
64. U.S. Preventive Services Task Force. Screening for abdominal aortic aneurysm:
recommendation statement. Ann Intern Med 2005; 142 : 198-202.
65. National Cholesterol Education Program ( NCEP_ Expert Panel on Detection,
Evaluation, and Treatment of High Blood Cholesterol in adults (Adult Treatment
Panel III). Third Report of the National Cholesterol Education Program (NCEP)
Expert Panel on Detection, Education and Treatment of High Blood Cholesterol in
Adults (Adult Treatment Panel III) final report. Circulation 2002; 106 : 3143-3421.
66. European Guidelines on Cardiovascular Disease Prevention in clinical practice.
Third Joint Task Force of European and other Societies on Cardiovascular Disease
Prevention in Clinical Practice. Eur J Cardio Prevention and Rehab 2003; 10 (
suppl 1); S1-78.
67. World Health Organization. Prevention of Cardiovascular Disease. Guidelines for
the assessment and management of Cardiovascular Risk. Geneva 2007; WHO
Press.
68. British Heart Foundation. European Cardiovascular Disease Statistics. London.
British Heart Foundation 2000.
40
69. Sans S, Kesteloot H, Kromhout D. The burden of cardiovascular diseases mortality

in Europe. Task Force of the European Society of Cardiology on Cardiovascular
Mortality and Morbidity Statistics in Europe. Eur Heart J 1997; 18 : 1231-48.
70. Atsma, F; Bartelink, MLEL; Grobbee, DE et al. Postmenopausal status and early
menopause as independent risk factors for cardiovascular disease: a meta-analysis
.Menopause 2006; 13 : 265-279.
71. Rossouw JE, Anderson GL, Prentice RL et al. Risks and benefits of estrogen plus
progestin in healthy postmenopausal women: principal results From the Womens
Health Initiative randomized controlled trial. JAMA 2002; 288 : 321-33.
72. Mohandas B, Mehta JL. Lessons from hormone replacement therapy trials for
primary prevention of cardiovascular disease. Curr Opin Cardionl 2007; 22 :
434-42
73. Hulley S, Grady D, Bush T et al. for the Heart and Estrogen/progestin Replacement
Study Research Group. Randomized trial of estrogen plus progestin for secondary
prevention of coronary heart disease in postmenopausal women. JAMA 1998; 280
: 605 13.
74. Grady D, Herrington D, Bittner V et al. Cardiovascular disease outcomes during
6.8 years of hormone therapy. Heart and Estrogen/progestin Replacement Study
follow-up ( HERS II). JAMA 2002 ; 288: 49-57.
75. Lobo RA Surgical menopause and cardiovascular risks. Menopause 2007;14(3):
562-566
76. Marenberg ME, Risch N, Berkman LF et al. Genetic susceptibility to death from
coronary heart disease in a study of twins. N Engl J Med 1994; 330 : 1041-6.
77. Lloyd- Jones DM, Nam BH, DAgostino RB Sr et al. Parental cardiovascular disease
as a risk factor for cardiovascular disease in middle aged adults: a prospective
study of parents and offspring. JAMA 2004; 291 : 2204-11.
78. Arnett DK, Baird AE, Barkley RA et al. Relevance of Genetics and Genomics
for Prevention and Treatment of Cardiovascular Disease: A Scientific Statement
From the American Heart Association Council on Epidemiology and Prevention,
the Stroke Council, and the Functional Genomics and Translational Biology
Interdisciplinary Working Group. Circulation 2007; 115 : 2878 - 2901.
79. Chow K, Pell ACH , Walker A et al. Families of patients with premature coronary
heart disease: an obvious but neglected target for primary prevention Br Med
J2007; 335 : 481 - 485.
80. Bittner V. Perspectives on Dyslipidemia and coronary heart disease in women. J
Am Coll Cardiol 2005; 46 : 1628-35.
81. Rich-Edwards JW, Manson JE, Hennekens CH et al. The primary prevention of
coronary heart disease in women. N Engl J Med 1995; 332 : 1758-66.
82. Stangl V, Baumann G, Stangl K.Coronary atherogenic risk factors in women Eur
Heart J 2002; 23 : 1738-1752.
83. Orth-Gomer K, Mittleman MA, Schenck-Gustafsson K et al. Lipoprotein (a) as a
determinant of coronary heart disease in young women. Circulation 1997; 95 : 329
34
84. Criqui MH, Heiss G, Cohn R et al. Plasma triglyceride level and mortality from
coronary heart disease. N Engl J Med 1993; 328 : 1220-25.
85. Hokanson JE, Austin MA. Plasma triglyceride level as a risk factor for cardiovascular
disease independent of high density lipoprotein level: a met-analysis of population
based prospective studies. J Cardiovasc Risk 1996; 3 : 213-9.
86. Knopp RH, Broyles FE, Bonet B et al. Exaggerated lipoprotein abnormalities
in diabetic women as compared to diabetic men: Possible significance for
atherosclerosis. In : Wenger NK, Speroff L, Packard B eds. Cardiovascular Health
and Disease in Women Greenwich, CT:Le Jacq Communications; 1993: 131-8.
41
87. NHMS III Conference Proceedings, Nov 2007, Putrajaya

88. Kotchen JM, Mackean HE, Kotchen TA. Blood pressure trends with ageing.
Hypertension 1982; 4 : III-128 - III-134.
89. Hajjar I, Kotchen TA. Trends in prevalence, awareness, treatment and control of
hypertension in the United States,1988-2000. JAMA 2003; 290 : 199-206.
90. Saltzberg S, Stroh JA, Frishman WH. Isolated systolic hypertension in the elderly:
pathophysiology and treatment. Med Clin North Am 1988; 72 : 523-547
91. Robitaille NM. Hypertension in women. Can J Cardiol 1996; 12 (suppl D); 6D-8D.
92. Staessen JA, Ginocchio G et al. Conventional and ambulatory blood pressure
and menopause in a prospective population study. J Hum Hypertens 1997; 11 :
507-514.
93. Levy D, Garrison RJ, Savage DD, Kannel WB, Castelli WP. Prognostic implications
of echocardiographically determined LV mass in the Framingham heart study. N
Engl J Med. 1990; 322 :15611566.
94. Liao Y, Cooper RS, Mensah GA et al. Left Ventricular Hypertrophy has a greater
impact on survival in women than in men. Circulation. 1995; 92 : 805-810.
95. Antikainen RL, Grodzicki T, Beevers DG et al for the Department of Health and
Social Security Hypertension Care Computer Project ( DHCCP). Left ventricular
hypertrophy determined by SokolowLyon criteria: a different predictor in women
than in men? J Hum Hypertens 2006; 20 : 451-9.
96. MacMahon S, Peto R, Cutler J et al. Blood pressure, stroke, and coronary heart
disease, part I: prolonged differences in blood pressure: prospective observational
studies corrected for the regression dilution bias. Lancet 1990; 335 : 765774.
97. Izzo JL Jr, Levy D, Black HR. Clinical Advisory Statement. Importance of systolic
blood pressure in older Americans. Hypertens 2000;35 : 1021-1024.
98. Lewington S, Clarke R,Qizilbash N et al. Age specific relevance of usual blood
pressure to vascular mortality: a meta-analysis of individual data for one million
adults in 61 prospective studies. Lancet 2002; 360 : 1903-13.
99. Prisant LM, Szerlip HM, Mulloy LL. Fibromuscular Dysplasia: An Uncommon Cause
of Secondary Hypertension. J Clin Hypertens 2006; 8 : 894898.
100. Myers MG,Reeves RA. White coat effect in treated hypertensive patients: sex
differences. J Hum Hypertens 1995; 9 : 729-33.
101. Hanes DS. Strategies for the treatment of hypertension in postmenopausal women.
J Clin Hypertens 1999; 1 : 62-71.
102. Rosenthal T, Oparil S. Hypertension in women. J Hum Hypertens 2000; 14 :
691-704.
103. Weir RJ, Briggs E, Mack A et al. Blood Pressure in women taking oral contraceptives
Br Med J 1974; 5907 : 533535.
104. Calhoun DA, Oparil S. Gender and Blood Pressure. Hypertension Primer. In : Izzo
JL Jr, Black HR (eds). The Essentials of High Blood Pressure. 2nd Ed. American
Heart Association: Baltimore Md. Lippincott Williams & Wilkins, 1999; 229-32.
105. Bellamy L, Casas J-P, Hingorani A-D et al. Pre-eclampsia and risk of cardiovascular
disease and cancer in later life: systematic review and meta-analysis. Br Med J
2007 335:974-977.
106. National Health & Morbidity Survey II Report 1996, Public Health Institute, Ministry
of Health Malaysia.
107. Mustaffa E, Bebakar WMW, SP Chan et al. Current status of Diabetic Management
in Malaysia. J Asean Fed Endocrine Soc 1998; 16: 2:(Suppl): 1-13.
108. Kannel WB, McGee DL. Diabetes and cardiovascular disease. The Framingham
study. JAMA 1979; 241 : 20352038.
42
109. Gu K, Cowie CC, Harris MI. Diabetes and decline in heart disease mortality in US
adults. JAMA. 1999; 281 : 1291-7.
110. Lee WL, Cheung AM, Cape D, Zinman B. Impact of diabetes on coronary artery
disease in women and men: a meta analysis of prospective studies. Diabetes Care
2000; 23 : 962-8.
111. Orchard TJ. The impact of gender and general risk factors on the occurrence of
atherosclerotic vascular disease in non-insulin-dependent diabetes mellitus. Ann
Med 1996; 28 : 323-33.
112. Laing SP, Swerdlow AJ, Slater SD et al. The British Diabetic Association Cohort
Study II: cause specific mortality in patients with insulin treated diabetes. Diabet
Med 1999; 16 : 466-71.
113. Huxley R, Barzi F, Woodward M .Excess risk of fatal coronary heart disease
associated with diabetes in men and women: meta-analysis of 37 prospective
cohort studies. Br Med J2006; 332 : 73-78.
114. Gregg EW, Gu Q, Cheng YJ et al. Mortality Trends in Men and Women with
Diabetes, 1971 to 2000, Ann Intern Med 2007; 147: 149-57).
115. The DECODE Study Group Consequences of the new diagnostic criteria for
diabetes in older men and women. DECODE Study (Diabetes Epidemiology:
Collaborative Analysis of Diagnostic Criteria in Europe). Diabetes Care 1999; 22 :
16671671.
116. Barr ELM, Zimmet PZ, Welborn TA et al. Risk of Cardiovascular and All-Cause
Mortality in Individuals With Diabetes Mellitus, Impaired Fasting Glucose, and
Impaired Glucose Tolerance.The Australian Diabetes, Obesity, and Lifestyle Study
(AusDiab). Circulation. 2007;116 : 151-157
117. Alberti KG, Zimmet P, Shaw J. IDF Epidemiology Task Force Consensus Group. The
metabolic syndrome-a new world-wide definition. Lancet 2005; 366 : 1059-62.
118. National Cholesterol Education Program. Third Report of the National Cholesterol
Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment
of High Blood Cholesterol in Adults (Adult Treatment Panel III) Final Report.
Circulation 2002; 106 : 3143-3421.
119. Despres J-P, Lemieux I. Abdominal obesity and metabolic syndrome. Nature 2006;
444 : 881-887.
120. Haffner SM.Abdominal adiposity and cardiometabolic risk: do we have all the
answers? Am J Med 2007;120 (9 Suppl 1) : S10-6.
121. Musso G, Gambino R, Bo S et al. Should nonalcoholic fatty liver disease be included
in the definition of metabolic syndrome? A cross-sectional comparison with ATP III
criteria in nonobese nondiabetic subjects. Diabetes Care Publish Ahead of Print,
published online on December 4, 2007 as dc07-1526.
122. Bogers RP, Bemelmans WJE, Hoogenveen RT et al for the BMI-CHD Collaboration
Investigators. Association of overweight with increased risk of Coronary Heart
Disease Partly independent of Blood Pressure and Cholesterol Levels: A Metaanalysis of 21 Cohort Studies Including More than 300 000 Persons. Arch Intern
Med2007; 167 : 1720 - 8.
123. Manson JE, Willet WC, Stampfer MJ et al. Body weight and mortality among
women. N Engl J Med 1995; 333 : 677-85
124. Lim TO, Ding LM, Zaki M et al. Distribution of body weight, height and body mass
index in a national sample of Malaysian adults. Med J Mal 2000; 55 : 108-28.
125. WHO Expert Consultation. Appropriate body-mass index for Asian populations and
its implications for policy and intervention strategies. Lancet 2004;363 : 15763.
126. Asia Pacific Cohort Studies Collaboration. Body mass index and cardiovascular
disease in the Asia-Pacific Region: an overview of 33 cohorts involving 310 000
participants. Int J Epidem 2004; 33 : 751-758.
43
127. Jee SH, Pastor- Barriuso R, Appel LJ et al. Body Mass Index and Incident
Ischaemic Heart Disease in South Korean Men and Women. Am J Epidem 2005;
162 : 42-48.
128. Deurenberg-Yap M, Schmidt G, van Staveren WA, Deurenberg P. The paradox
of low body mass index and high body fat percent among Chinese, Malays and
Indians in Singapore.Int J Obes2000;24:1011-1017.
129. Li TY, Rana JS, Manson JE et al. Obesity as compared with physical activity in
predicting risk of coronary heart disease in women. Circulation 2006; 113 : 499
506.
130. Colditz GA, Willett WC, Rotnitzky A et al. Weight Gain as a Risk Factor for Clinical
Diabetes Mellitus in Women. Ann Intern Med 1995; 122 : 481-6.
131. Jousilahti P, Tuomilehto J, Vartiainen E et al. Body weight, cardiovascular risk
factors and coronary mortality. 15 year follow-up of middle aged men and women
in Eastern Finland. Circulation 1996; 93 : 1372-79.
132. Lissner L, Odell PM, DAgostino RB et al. Variability of body weight and health
outcomes in the Framingham population. N Engl J Med 1991; 324 : 1839 44.
133. Folsom AR, French SA, Zheng W et al. Weight variability and mortality: the Iowa
Womens Health Study. Int J Obes Relat Metab Disord 1996; 20 : 704 -9
134. Scottish Intercollegiate Guidelines Network. The benefits of weight loss. In: Network
SIG, ed. Obesity in Scotland: Integrating Prevention with Weight Management.
Edinburgh: Scottish Intercollegiate Guidelines Network; 1996; 12-15.
135. Willet WC, Green A, Stampfer MJ et al. Relative and absolute excess risks of
coronary heart disease among women who smoke cigarettes. N Engl J Med 1987;
317 : 1303-9.
136. Prescott E, Hippe M, Schnohr P et al. Smoking and risk of myocardial infarction in
women and men : longitudinal population study. Br Med J 1998;316 : 1043-47.
137. Dunn NR, Faragher B, Thorogood M et al. Risk of myocardial infarction in young
female smokers. Heart 1999; 82 : 581-583
138. WHO Collaborative Study of Cardiovascular Disease and Steroid Hormone
Contraception. Acute myocardial infarction and combined oral contraceptives:
results of an international multicentre case-control study. Lancet. 1997; 349 :
12021209.
139. Keeling D. Combined oral contraceptives and the risk of myocardial infarction. Ann
Med 2003; 35 : 413-8.
140. Palmer JR, Rosenberg L, Shapiro S. Low yield cigarettes and the risk of nonfatal
myocardial infarction in women. N Engl J Med 1989; 320 : 1569-1573.
141. Andersen LB, Schnohr P, Schroll M, Hein HO. All-cause mortality associated with
physical activity during leisure time, work, sports, and cycling to work. Arch Intern
Med 2000; 160 : 1621-1628.
142. Lissner L, Bengtsson C, Bjrkelund C, Wedel H. Physical activity levels and
changes in relation to longevity: a prospective study of Swedish women. Am J
Epidemiol. 1996;143 : 54-62.
143. Barengoa NC, Hub GC, Lakkaa TA. Low physical activity as a predictor for total and
cardiovascular disease mortality in middle-aged men and women in Finland. Eur
Heart J 2004; 25 : 22042211.
144. Hu G, Tuomilehto J, Borodulin K , Jousilahti P. The joint associations of occupational,
commuting, and leisure-time physical activity, and the Framingham risk score on
the 10-year risk of coronary heart disease. Eur Heart J 2007; 28 : 492-498.
145. I-Min Lee, Rexrode KM, Cook NR et al. Physical Activity and Coronary Heart
Disease in Women. Is No Pain, No Gain Passe? JAMA 2001; 285 : 1447-54.
146. Hu FB, Willet WC, Li T et al. Adiposity as compared with physical activity in
predicting mortality among women. N Engl J Med 2004; 351 : 2694-2703.
44
147. Gibbons LW, Blair SN,Cooper KH,Smith M. Association between coronary heart
disease risk factors and physical fitness in healthy adult women. Circulation 1983;
67 : 977-83.
148. LaMonte MJ, Eisenman PA, Adams TD et al. Cardiorespiratory Fitness and
Coronary Heart Disease Risk Factors. The LDS Hospital Fitness Institute Cohort.
Circulation. 2000; 102 : 1623-1628.
149. Hennekens CH, Evans DA, Castelli WP et al. Oral contraceptive use and fasting
triglyceride, plasma cholesterol and HDL cholesterol. Circulation 1979; 60 : 486-9.
150. Gomes MPV, Deitcher SR. Risk of Venous Thromboembolic Disease Associated
With Hormonal Contraceptives and Hormone Replacement Therapy. A Clinical
Review Arch Intern Med.2004; 164 : 1965-1976.
151. Speroff L, DeCherney A and The Advisory Board for the New Progestins. Evaluation
of a new generation of oral contraceptives. Obstet & Gyne 1993; 81 : 1034-1047.
152. Rosenberg L, Palmer JR, Rao S, Shapiro S. Low dose oral contraceptive use and
the risk of myocardial infarction. Arch Intern Med 2001; 161 : 1065-70.
153.The Womens Health Initiative Steering Committee. The Womens Health
Initiative Randomized Controlled Trial Effects of Conjugated Equine Estrogen in
Postmenopausal Women With Hysterectomy. JAMA.2004; 291 : 1701-1712.
154. Castelnuovo AD, Costanzo S, Bagnardi V et al. Alcohol Dosing and Total Mortality
in Men and Women. An Updated Meta-analysis of 34 Prospective Studies. Arch
Intern Med.2006; 166 : 2437-2445.
155. Fuchs CS, Stampfer MJ, Colditz GA et al. Alcohol consumption and mortality
among women. N Engl J Med.. 1995; 332 : 1245-1250.
156. Corrao G, Bagnardi V, Zambon A, La Vecchia C. A meta-analysis of alcohol
consumption and the risk of 15 diseases. Prev Med. 2004; 38 : 613-619.
157. DAgostino Sr RB, Vasan RS, Pencina MJ et al. General Cardiovascular Risk
Profile for Use in Primary Care. The Framingham Heart Study. Circulation Jan
2008; doi:10.1161
158. Hippisley Cox J, Coupland C, Vinogradova Y et al. Derivation and validation
of QRISK, a new cardiovascular disease risk score for the United Kingdom:
prospective open cohort study. Br. Med J 2007; 335 : 136 141.
159. Woodward M, Brindle P., Tunstall Pedoe H et al for the SIGN Group on Rsk
Estimation. ASdding social de[privation and family history to cardiovascular risk
assessment: the ASSISN score from the Scottish Heart Health Extended Cohort
(SHHEC) Heart 2007; 93 : 172-176.
160. Bastuji-Garin S, Deverly A, Moyse D et al. on behalf of the INSIGHT committees
and Investigators. The Framingham prediction rule is not valid in a European
population of treated hypertensive patients. J Hypertens 2002; 20 : 1973 80.
161. Liu J, Hong Y, DAgostino RB Sr et al. Predictive value for the Chinese population of
the Framingham CHD risk assessment tool compared with Chinese Multi-Provincial
Cohort Study. JAMA 2004; 291: 2591-99.
162. Sibley C, Blumenthal RS, Bairey Merz CN et al. Limitations of current cardiovascular
disease risk assessment strategies in women. J Womens Health (Larchmt) 2006;
15 : 54-56.
163. Lloyd-Jones DM, Leip EP, Larson MG et al. Prediction of lifetime risk for
cardiovascular disease by risk factor burden at 50 years of age. Circulation. 2006;
113 : 791-798.
164. Smith SC, Jr, Greenland P, Grundy SM. Prevention Conference V : Beyond
Secondary Prevention : Identifying the High-Risk Patient for Primary Prevention :
Executive Summary. Circulation, Jan 2000; 101: 111 - 116.
165. Hurst W. The Heart, arteries and veins. 1st Ed. New York. NY:McGraw-Hill
45
166. Yusuf S, Hawken S, Ounpuu S, on behalf of the INTERHEART Study Investigators.

Effect of potentially modifiable risk factors associated with myocardial infarction in
52 countries (the INTERHEART study): case-control study. Lancet 2004; 364 : 937952.
167. Vasan RS, Sullivan LM, Wilson PWF et al. Relative Importance of Borderline and
Elevated Levels of Coronary Heart Disease Risk Factors. Ann Intern Med 2005;
142 : 393-402.
168. Stampfer MJ, Hu FB, Manson JE et al. Primary prevention of coronary heart
disease in women through diet and lifestyle. N Engl J Med 2000; 343 : 16-22.
169. Appel LJ, Moore TJ, Obarzanek E et al for the DASH Collaborative Research
Group. A Clinical Trial of the Effects of Dietary Patterns on Blood Pressure. N Engl
J Med 1997; Volume 336 : 1117-1124.
170. Lichtenstein, A. H., Appel, L. J., Brands et al Diet and Lifestyle Recommendations
Revision 2006: A Scientific Statement From the American Heart Association
Nutrition Committee. 2006; Circulation 114 : 82-96.
171. DeLorgeril M, Salen P, Martin JL et al. Mediterranean diet, traditional risk factors,
and the rate of cardiovascular complications after myocardial infarction; final report
of the Lyon Diet Heart Study. Circulation 1999; 99 : 779-85.
172. Wang L, Gaziano JM, Liu S et al. Whole- and refined-grain intakes and the risk of
hypertension in women. 2007; Am J Clin Nutr; 86 : 472-479.
173. Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after
myocardial infarction: results of the GISSI Prevenzione trial, Gruppo Italiano per
lo Studio della Suprovvivenza nell infarto miocardico. Lancet 1999; 354 : 447-55.
174. Dauchet L, Amouyel P, Hercberg S, Dallongeville, J. Fruit and Vegetable
Consumption and Risk of Coronary Heart Disease: A Meta-Analysis of Cohort
Studies. 2006 J. Nutr. 136: 2588-2593.
175. Kris- Etherton PM, Harris WS. Aprel LJ for the Nutrition Committee. Fish
consumption, fish oil, omega-3-fatty acids and cardiovascular disease. Circulation
2002; 106 : 2747-57.
176. Oh K, Hu FB, Manson JE et al Dietary fat intake and risk of coronary heart disease
in women: 20 years of follow-up of the Nurses Health Study. Am J Epidemiol. 2005;
161 : 672-679.
177. Boniface DR, Tefft ME. Dietary fats and 16 year coronary heart disease mortality in
a cohort of men and women in Great Britain. Eur J Clin Nutr 2002; 56 : 786-792.
178. Whelton SK, Appel LJ, Espeland MA et al. Sodium restriction and weight loss in the
treatment of hypertension in older persons: a randomised controlled trial of nonpharmacologic intervention in the elderly (TONE). TONE Collaborative Research
Group. JAMA 1998; 279 : 839-846.
179. Effects of weight loss and sodium reduction intervention on blood pressure and
hypertension incidence in overweight people with high-normal blood pressure: The
Trials of Hypertension Prevention, Phase II. The Trials of Hypertension Prevention
Collaborative Research Group. Arch Intern Med 1997;157 : 657-667.
180. Shephard RJ, Balady GJ. Exercise as cardiovascular therapy. Circulation 1999; 99
: 963-72.
181. Critchley JA, Capewell S. Mortality risk reduction associated with smoking cessation
in patients with coronary heart disease : a systematic review. JAMA 2003; 290 :
86- 97.
182. Collaborative meta-analysis of randomised trials of antiplatelet therapy for
prevention of death, myocardial infarction, and stroke in high risk patients.
Antithrombotic Trialists Collaboration. Br Med J 2002; 324 : 71-86.
46
183. Pearson TA, Blair SN, Daniels SR, et al. AHA Guidelines for primary prevention
of cardiovascular disease and stroke. 2002 update: consensus panel guide
to comprehensive risk reduction for adult patients without coronary or other
atherosclerotic vascular diseases. American Heart Association Science Advisory
and Coordinating Committee. Circulation 2002; 106 : 388-391.
184. Ridker PM, Cook NR, Lee I-M, et al. A randomized trial of low-dose aspirin in the
primary prevention of cardiovascular disease in women. N Engl J Med 2005; 352 :
1293-1304.
185. Malaysian Clinical Practice Guidelines on Dyslipidaemia. 3rd ed 2003. available at
www.acadmed.com.my
186. Heart Protection Study Collaborative Study Group. MRC/BHF. Heart Protection
Study of cholesterol lowering with simvastatin in 20536 high- risk individuals: a
randomized placebo controlled trial. Lancet 2002; 360 : 7-22.
187. LaRosa JC, Grundy SM, Waters DD et al. Intensive lipid lowering with atorvastatin
in patients with stable coronary disease. N Engl J Med 2005; 352 : 14251435.
188. Nissen SE, Tuzcu EM, Schoenhagen P et al. Effect of intensive compared with
moderate lipid-lowering therapy on progression of coronary atherosclerosis: a
randomized controlled trial. JAMA 2004; 291 : 10711080.
189. Rubins HB, Robins SJ, Collins D et al. for the Veteran Affairs High density
Lipoprotein Cholesterol Intervention Trial Study Group. Gemfibrozil for the
secondary prevention of coronary heart disease in men with low levels of highdensity lipoprotein cholesterol. N Engl J Med 1999; 341 : 410-8.
190. Malaysian Clinical Practice Guidelines on Hypertension, 3rd ed 2008. available at
www.acadmed.com.my
191. Lewis CE; Grandits A; Flack J et al. Efficacy and tolerance of antihypertensive
treatment in men and women with stage 1 diastolic hypertension. Results of the
Treatment of Mild Hypertension Study. Arch Intern Med, 1996; 156 : 377-385.
192. Nestel PJ, Clifton PM, Noakes M et al. Enhanced blood pressure response
to dietary salt in elderly women, especially those with small waist : hip ratio. J
Hypertens. 1993; 11 : 13871394.
193. Lewis CE. Characteristics, treatment of hypertension in women: a review of the
literature. Am J Med Sci 1996; 311 : 193199.
194. Os I, Bratland B, Dahlof B et al. Female sex as an important determinant of lisinopril
induced cough. Lancet 1992; 339 : 372-3.
195. Poobalan AS, Aucott LS, Smith WCS et al. Long term weight loss effects on all
cause mortality in overweight/obese populations. Complications of obesity. Obes
Rev 2007; 8 : 503-13.
196. ACC/AHA/ESC 2006 guidelines for the management of patients with atrial
fibrillation - executive summary. A report of the American College of Cardiology/
American Heart Association Task Force on Practice Guidelines and the European
Society of Cardiology Committee for Practice Guidelines (Writing Committee to
Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation).
J Am Coll Cardiol 2006; 48 : 854-906.
197. Lonn E, Bosch J, Yusuf S et al for the HOPE and HOPE-TOO Trial Investigators.
Heart Outcome Prevention Evaluation & Heart Outcome Prevention Evaluation
The Ongoing Outcome Trial. Effects of long term vitamin E supplementation on
cardiovascular event and cancer : a randomized controlled trail. JAMA 2005; 293
: 1338-47.
198. Heart Protection Study Collaboration Group. MRC/BHF Heart protection study of
antioxidant vitamin supplementation in 20,536 high risk individuals: a randomized
placebo controlled trail. Lancet 2002; 360 : 23-33.
47
APPENDIX 1: ALCOHOL CONTENT OF COMMON SPIRITS

Wine
125ml (small glass)
175ml
(standard
glass)
12%
2.1 units
1.5 units
14%
1.75 units
2.45 units
Beer
Half Pint
4%
1.1 units
5%
1.4 units
330ml
bottle
Pint
2.2 units
1.7 units
2.8 units
Spirits
25ml (single)
50ml
(double)
40%
1 unit
2 units
Adapted from the UK government guidelines on alcohol consumption
48
APPENDIX 2: FRAMINGHAM RISK SCORE FOR

ASSESSMENT OF CVD RISK
APPENDIX 2A: CVD POINTS FOR WOMEN*
Points
Age,y
HDL-C
TC
-3
<120
-2
1.6+
-1
1.3-1.6
30-34 1.2-<1.3
1
2
SBP (not SBP

Smoker Diabetes
treated) (treated)
<120
<4.2
120-129
No
0.9-<1.2 4.2-<5.2 130-139

35-39
<0.9
140-149 120-129
5.2-<6.3
40-44
45-49
130-139
6.3-<7.4 150-159
>7.4
150-159
50-54
55-59
60-64
10
65-69
11
70-74
12
75+
Points
allotted
Grand Total :_____________points
Yes
Yes
160+ 140-149
49
No
160+
APPENDIX 2B: CVD RISK FOR WOMEN*

Total Points
10 year Risk %
Total Points
10 year Risk %
<-2
-1
0
1
2
3
4
5
6
7
8
9
<1
1.0
1.2
1.5
1.7
2.0
2.4
2.8
3.3
3.9
4.5
5.3
10
11
12
13
14
15
16
17
18
19
20
21+
6.3
7.3
8.6
10.0
11.7
13.7
15.9
18.5
21.5
24.8
28.5
>30
APPENDIX 2C: HEART AGE/VASCULAR AGE FOR

WOMEN*
Points
Heart age, y
<1
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15+
<30
31
34
36
39
42
45
48
51
55
59
64
68
73
79
>80
To determine a womens CVD risk, calculate in order:

1. Grand Total CVD points
2. 10 year Risk of CVD
3. Heart Age/Vascular Age for Women
*Adapted from DAgostino RB et al I157
50
APPENDIX 3: SUGGESTED DRUG THERAPY FOR

DYSLIPIDAEMIA
Lipid Values
Initial drug
Suggested Addition
(in order of preference)
Resin
Ezetimibe
Fibrates
Nicotinic Acid
LDL-C >3.4mmol/l
TG <2.3mmo/l
Statins
LDL-C >3.4mmol/l
TG : 2.3 - 4.5mmol/l
Statins
Fibrates
Nicotinic Acid
HDL-C <1.0mmol/l
TG <4.5mmol/l
If:
LDL-C <2.6mmol/l
Fibrates
If:
LDL-C >2.6mmol/l
Statins
Nicotinic Acid
Statins
Fibrates
Nicotinic Acid
TG >4.5mmol/l
Fibrates
Nicotinic Acid
Statins
Adapted from Malaysian CPG on Dyslipidaemia 2003185
51
APPENDIX 4: MANAGEMENT OF HYPERTENSION

APPENDIX 4A: RISK STRATIFICATION OF
HYPERTENSION
Co-existing
Condition
No RF
No TOD
No TOC
TOD
or
RF (1 2)
No TOC
BP Levels
(mmHg)
TOC
Previous MI
or
or
RF (3)
Previous stroke
or
or
Clinical
Diabetes
atherosclerosis
SBP
Low
120 139
and/or
DBP 80 89
Medium
High
Very high
SBP
Low
140 159
and/or
DBP 90 99
Medium
High
Very high
SBP
160 179
and/or
DBP
100 109
Medium
High
Very high
Very high
SBP
180 209
and/or
DBP
110 119
High
Very high
Very high
Very high
SBP 210
and/or
DBP 120
Very high
Very high
Very high
Very high
TOD = Target organ damage (LVH, retinopathy, proteinuria)

TOC = Target organ complication (heart failure, renal failure)
RF = additional risk factors (smoking, TC >6.5mmol/L, family
history of premature vascular disease)
Clinical atherosclerosis (CHD, carotid stenosis, peripheral vascular
disease)
Adapted from Malaysian CPG on Hypertension, 3rd ed, 2008190
52
APPENDIX 4B: RECOMMENDATIONS FOR FOLLOW

UP BASED ON INITIAL BP
Initial BP (mmHg)
Systolic
<130
130-139
140-159
160-179
Diastolic
and
and
and/or
and/or
<85
85-89
90-99
100-109
180-209 and/or 110-119

210
and/or 120
Follow-up recommended
to confirm diagnosis and/
or review response to
treatment
Recheck in one year
Recheck within 3-6 months
Confirm within two months
Evaluate within one month
and treat if confirmed
Evaluate within one week and
treat if confirmed
Initiate drug treatment
immediately
Adapted from Malaysian CPG on Hypertension,3rd ed, 2008190
APPENDIX 4C: EFFECTIVE ANTI HYPERTENSIVE

COMBINATIONS
Effective
combinations
Comments
-blockers + diuretics
Benefits proven in the elderly, costeffective. However, may increase risk

of new onset diabetes
-blockers + CCBs
Relatively cheap, appropriate for

concurrent CHD
CCBs + ACEIs/ARBs
Appropriate for concurrent

dyslipidaemias and diabetes mellitus
ACEIs + diuretics
Appropriate for concurrent heart

failure, diabetes mellitus and stroke
ARBs + diuretics
Appropriate for concurrent heart

failure and diabetes mellitus
Adapted from Malaysian CPG on Hypertension,3rd ed, 2008190
53
APPENDIX 5: AUDIT OF CLINICAL DIABETES

GREEN BOOK
Hospital/ Health Clinic: __________________________
Name of patient: _______________________________
D.O.B: _______________________________________
Date when diabetes was diagnosed: _______________
estimate/presumed
Date of the
Result of the most
Not
most recent
recent examination
done
examination
Criteria
Height
cm
Weight
kg
Waist
circumference
Body Mass Index
(BMI)
cm
kg/m2
Blood Pressure
mmHg
FBS, RBS or
2HPP
mmol/L
HbA
1c
Lipid
profile
Type of practice: FMS/MO/AMO

IC No: ____________________
Sex: Male / Female
Ethnic group: ______________
TC:
mmol/L
TG:
mmol/L
HDL:
mmol/L
LDL:
mmol/L
Creatinine
mol/l
Urine
microalbumin
Normal / Abnormal
Urine protein
Present / Absent
Fundoscopy
Normal / Abnormal
Examination of
feet
Normal / Abnormal
ECG
Normal / Abnormal
* Estimate/presumed: If date not known, enter 30/06/yyyy and mark the box.
54
ACKNOWLEDGMENTS
The committee of this guideline would like to express their gratitude
and appreciation to the following for their contribution:
Technical Advisory Committee, Clinical Practice Guidelines,
Ministry of Health for their valuable input and feedback
Panel of external reviewers who reviewed the draft
DISCLOSURE STATEMENT
The panel members have no potential conflict of interest to
disclose.
SOURCES OF FUNDING
This CPG was made possible by an unrestricted educational grant
from sanofi-aventis (M) Sdn Bhd.
55
56

Prevention of Cardiovascular Disease in Woman

Uploaded by

Document Information

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Prevention of Cardiovascular Disease in Woman

Uploaded by

Copyright:

Available Formats

MOH/P/PAK/171.

REVIEW OF THE GUIDELINES

Available on the following websites:

MESSAGE FROM THE DIRECTOR GENERAL OF HEALTH

Y.Bhg Tan Sri Datuk Dr Hj Mohd Ismail Merican

MEMBERS OF THE EXPERT PANEL

Senior Consultant Cardiologist

Expert Panel Members (in alphabetical order):

Dr Chan Siew Pheng

Senior Consultant Endocrinologist

Dr Ong Mei Lin

Senior Consultant Physician

Dr Sim Kui Hian

Senior Consultant Cardiologist

Dr Chia Yook Chin

Dr Lee Fatt Soon

COMMENTS FROM INTERNATIONAL REVIEWERS:

"My congratulations on an extremely well done Guideline

Professor of Medicine in the Division of Cardiology at

"These are wonderful - so well formatted and wonderful

Director Women's Heart Center

RATIONALE AND PROCESS OF GUIDELINE

comments. It was also sent to members of the American College of

Clinical Questions Addressed:

Period of Validity of the Guidelines:

Implementation of the Guidelines:

Continuous medical education and training of healthcare

Conditions for which there is evidence and/or

Conditions for which there is conflicting evidence

Weight of evidence/opinion is in favor of its

Usefulness/efficacy is less well established by

Conditions for which there is evidence and/or

Data derived from multiple randomized clinical

Data derived from a single randomized clinical trial

Only consensus of opinions of experts, case studies

KEY TO EVIDENCE STATEMENTS

Evidence obtained from at least one properly

Evidence obtained from well-designed controlled trials

Evidence obtained from multiple time series with

Opinions of respected authorities, based on clinical

Source from U.S./CANADIAN PREVENTIVE SERVICES TASK FORCE

At least one meta-analysis, systematic review, or RCT,

Evidence from well conducted clinical trials, directly

Evidence from expert committee reports, or opinions

Cardiovascular disease (CVD) is the main cause of death among

INTERVENTIONS TO PREVENT CARDIOVASCULAR

General Recommendations to all women

Level III, Grade C

Level II-1, Grade B

Maintain BMI 18.5 to

Level II-2, Grade B

Level II-2, Grade B

Treatment of specific risk factors

2. TYPES OF CARDIOVASCULAR DISEASE

3. CARDIOVASCULAR RISK FACTORS

4. TOTAL CARDIOVASCULAR RISK ASSESSMENT

5. RECOMMENDATIONS FOR PREVENTION

Alcohol content of common spirits

1. THE SCOPE OF THE PROBLEM

Figure 1A : Death among women due to Cardiovascular

* expressed as % of total female deaths

Figure 1B: Death among women due to Heart Disease and

** deaths in government hospitals only

2. TYPES OF CARDIOVASCULAR DISEASE