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
Secretary:

Senior Consultant Cardiologist Institute Jantung Negara, KL

Dr Jeyamalar Rajadurai

Consultant Cardiologist Subang Jaya Medical Centre, Selangor

Expert Panel Members (in alphabetical order):

Dr Chan Siew Pheng Dr Ong Mei Lin Dr Santha Kumari

Senior Consultant Endocrinologist University Malaya Medical Centre, KL Consultant Cardiologist Gleneagles Medical Centre, Penang Senior Consultant Physician Hospital Tengku Ampuan Rahimah, Selangor Senior Consultant Cardiologist Sarawak General Hospital, Sarawak Consultant Endocrinologist Hospital Putrajaya, Putrajaya

Dr Sim Kui Hian Dr Zanariah Hussein

III

External Reviewers:

Dr Aris Chandran

Consultant Physician Ipoh General Hospital Perak

Dr Chia Yook Chin

Consultant Physician University Malaya Medical Centre Kuala Lumpur

Dr Fatanah Ismail

Principle Assistant Director and Epidemiologist Disease Control Division Ministry of Health Malaysia Putrajaya

Dr Majdah bt Hj Mohamed
Principal Assistant Director Womens Health Department Public Health Division Ministry of Health Malaysia Putrajaya

Dr Lee Fatt Soon

Consultant Geriatrician Hospital Kuala Lumpur Kuala Lumpur

Dr Husni Hussain

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. Conditions for which there is conflicting evidence and/or divergence of opinion about the usefulness/ efficacy of a procedure/therapy. Weight of evidence/opinion is in favor of its usefulness/efficacy. Usefulness/efficacy is less well established by evidence/opinion 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 A B C 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

II

II-a II-b

III

Adapted from the American Heart Association and the European Society of Cardiology

VIII

KEY TO EVIDENCE STATEMENTS

LEVEL I II - 1 II - 2 Evidence obtained from at least one properly randomized controlled trial Evidence obtained from well-designed controlled trials without randomization Evidence obtained from well-designed cohort or casecontrol analytic studies, preferable from more than one center or research group 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 Opinions of respected authorities, based on clinical experience; descriptive studies and case reports; or reports of expert committees

II - 3

III

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 Grade I, Level C MOH Classification Level III, Grade C

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 Exercise a minimum of 30mins of moderate intensity exercises on most days of the week Maintain BMI 18.5 to <23kg/m2 and waist circumference <80cm Stop smoking 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

Grade I, Level B

Level II-1, Grade B

Grade I, Level B

Level II-2, Grade B

Grade I, Level B

Level II-2, Grade B

Treatment of specific risk factors

Grade I, Level A Grade I, Level B

Level 1, Grade A

Grade I, Level A Grade I, Level A Grade I, Level A

Level 1, Grade A Level 1, Grade A Level 1, Grade A

XI

Diabetes: HBA1c <6.5% LDL-C <2.6mmol/l TG <1.7mmol/l BP <130/80mmHg Aspirin: in patients with CVD 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

Grade I, Level A Grade I, Level A Grade I, Level A Grade I, Level A Grade I, Level B

Level 1, Grade A Level 1, Grade A Level 1, Grade A Level 1, Grade A Level 1, Grade A

Grade I, Level A

Level 1, Grade A

Grade I, Level B

Level 1, Grade A

Grade III,Level A Grade III,Level A

Level 1, Grade A Level 1, Grade A

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 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
XIII

1 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 10 10 11 11 12 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

23 23 24 24 26 30 30 30 31 31 31 31 32 32 32 32 33 33 33 33 34 34 35 35 35 37 48 49 49 50 50 51 52 52 53 53 54 55 55 55

4. TOTAL CARDIOVASCULAR RISK ASSESSMENT 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 REFERENCES APPENDIX 1 APPENDIX 2 Alcohol content of common spirits Framingham risk score for assessment of CVD Risk APPENDIX 2A CVD points for women APPENDIX 2B CVD risk for women APPENDIX 2C Heart age/Vascular age for women APPENDIX 3 Suggested drug therapy for dyslipidaemia APPENDIX 4 Management of Hypertension APPENDIX 4A Risk stratification of hypertension APPENDIX 4B Recommendations for follow up based on initial BP APPENDIX 4C Effective anti hypertensive combinations APPENDIX 5 Audit of clinical diabetes green book ACKNOWLEDGEMENTS DISCLOSURE STATEMENT SOURCES OF FUNDING

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

2.3.1 Presenting symptoms 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)

2.4.1 Presenting symptoms 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 menopausal 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. Postmenopausal 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 447 064 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
Fasting 2hr post-OGTT

DM
>7.0 >11.1

IFG
> 6.1 6.9

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

Overweight/ Obese
NHMS III

NHMS III NHMS II

NHMS III NHMS II

Males Females Overall

15.1% 17.9% 16.6%

29.7% 28.6% 29.1%

2.9% 5.7% 4.4%

10.1% 17.3% 14.0%

18.0% 23.6% 21.0%

39.8% 45.9% 43.1%

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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 >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

Blood Pressure Diabetes

Lipids

The above are seen in addition to psychological, physical and other metabolic benefits.
20

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.

3.9 SMOKING

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 secondary 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) 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 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. 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 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.
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.

5.1.1 Nutrition .

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.
2

and ideal waist Level II-2,

Grade B

Weight control can be achieved by restriction of total calorie intake and regular physical activity.
Grade I, Women Level B tobacco

5.1.4 Cigarette smoking should not smoke and should avoid environmental Level II-2, Grade B smoke181. 5.1.5 Aspirin in all women with Level I,

Grade I, Aspirin is indicated for secondary prevention Level A CHD and CHD risk equivalents182,183. Grade I, For primary Level B years184.

Grade A

prevention, aspirin is only beneficial in women >65 Level I,

Grade A

31

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 LDL-C HDL-C TG <2.6mmol/l with an option of <2.0mmol/l >1.0mmol/l <1.7mmol/l <2.3mmol/l <2.3mmol/l At Risk <3.4mmol/l Optimal Risk <4.1mmol/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. low HDL-C and Level I,
Grade A

Grade IIa, In patients who have normal LDL-C but have a Level B high TG, fibric acid derivatives may be used189.

The management of dyslipidaemia in women is as in the Malaysian Clinical Practice Guidelines on Dyslipidaemia, 2003185. (see Appendix 3) 5.2.2 Hypertension
Grade I, Level A The

5.2.2.1 Targets of Therapy target BP in most patients should be <140/85mmHg190. 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.

Level I, Grade A

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 BP LDL-C Lipids Fasting 2hr PP Target <6.5% <6.1mmol/L <7.8mmol/L <130/80 mmHg <2.6mmol/L With an option of <2.0mmol/L <1.7mmol/L >1.0mmol/L IIa, B I, A I, A I, A I, A I, A Grade, Level I, A Level, Grade I, A

TG HDL-C

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.
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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
Grade IIa, Level B

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

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.

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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.

Grade A Level I, Grade A

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 Hormone Replacement Therapy71,72,73,64,153
Grade III, Level A

36

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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.

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APPENDIX 1: ALCOHOL CONTENT OF COMMON SPIRITS Wine 12% 14% Beer 4% 5% Spirits 40% 125ml (small glass) 2.1 units 1.75 units Half Pint 1.1 units 1.4 units 1.7 units 330ml bottle 175ml (standard glass) 1.5 units 2.45 units Pint 2.2 units 2.8 units 50ml (double) 2 units

25ml (single) 1 unit

Adapted from the UK government guidelines on alcohol consumption

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APPENDIX 2: FRAMINGHAM RISK SCORE FOR ASSESSMENT OF CVD RISK APPENDIX 2A: CVD POINTS FOR WOMEN*
Points Age,y HDL-C TC SBP (not SBP Smoker Diabetes treated) (treated)

-3 -2 -1 0 1 2 3 4 5 6 7 8 9 10 11 12 Points allotted 50-54 55-59 60-64 65-69 70-74 75+ 40-44 45-49 35-39 1.6+ 1.3-1.6 30-34 1.2-<1.3 <4.2

<120

<120 120-129 No No

0.9-<1.2 4.2-<5.2 130-139 <0.9 5.2-<6.3 6.3-<7.4 150-159 >7.4 160+ 140-149 150-159 160+ 140-149 120-129 130-139 Yes Yes

Grand Total :_____________points

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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 <1 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15+ Heart age, y <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
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APPENDIX 3: SUGGESTED DRUG THERAPY FOR DYSLIPIDAEMIA

Lipid Values Initial drug Suggested Addition (in order of preference) Resin Ezetimibe Fibrates Nicotinic Acid Fibrates Nicotinic Acid

LDL-C >3.4mmol/l TG <2.3mmo/l

Statins

LDL-C >3.4mmol/l TG : 2.3 - 4.5mmol/l HDL-C <1.0mmol/l TG <4.5mmol/l If: LDL-C <2.6mmol/l If: LDL-C >2.6mmol/l

Statins

Fibrates Statins

Statins Nicotinic Acid Fibrates Nicotinic Acid Nicotinic Acid Statins

TG >4.5mmol/l

Fibrates

Adapted from Malaysian CPG on Dyslipidaemia 2003185

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APPENDIX 4: MANAGEMENT OF HYPERTENSION APPENDIX 4A: RISK STRATIFICATION OF HYPERTENSION

Co-existing Condition BP Levels (mmHg) SBP Low 120 139 and/or DBP 80 89 SBP Low 140 159 and/or DBP 90 99 SBP 160 179 and/or DBP 100 109 SBP 180 209 and/or DBP 110 119 SBP 210 and/or DBP 120 No RF No TOD No TOC TOD or RF (1 2) No TOC TOC Previous MI or or RF (3) Previous stroke or or Clinical Diabetes atherosclerosis

Medium

High

Very high

Medium

High

Very high

Medium

High

Very high

Very high

High

Very high

Very high

Very high

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

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APPENDIX 4B: RECOMMENDATIONS FOR FOLLOW UP BASED ON INITIAL BP

Initial BP (mmHg) 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

Systolic
<130 130-139 140-159 160-179

Diastolic

and <85 and 85-89 and/or 90-99 and/or 100-109 110-119

180-209 and/or 210

and/or 120

Adapted from Malaysian CPG on Hypertension,3rd ed, 2008190

APPENDIX 4C: EFFECTIVE ANTI HYPERTENSIVE COMBINATIONS

Effective combinations -blockers + diuretics Comments Benefits proven in the elderly, costeffective. However, may increase risk of new onset diabetes Relatively cheap, appropriate for concurrent CHD Appropriate for concurrent dyslipidaemias and diabetes mellitus Appropriate for concurrent heart failure, diabetes mellitus and stroke Appropriate for concurrent heart failure and diabetes mellitus

-blockers + CCBs CCBs + ACEIs/ARBs ACEIs + diuretics ARBs + diuretics

Adapted from Malaysian CPG on Hypertension,3rd ed, 2008190

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APPENDIX 5: AUDIT OF CLINICAL DIABETES GREEN BOOK

Hospital/ Health Clinic: __________________________ Name of patient: _______________________________ D.O.B: _______________________________________ Date when diabetes was diagnosed: _______________ estimate/presumed Type of practice: FMS/MO/AMO IC No: ____________________ Sex: Male / Female Ethnic group: ______________

Criteria Height Weight Waist circumference Body Mass Index (BMI) Blood Pressure FBS, RBS or 2HPP HbA
1c

Date of the Result of the most Not most recent recent examination done examination cm kg cm kg/m2 mmHg mmol/L % TC:

mmol/L mmol/L mmol/L mmol/L

mol/l Normal / Abnormal Present / Absent Normal / Abnormal Normal / Abnormal Normal / Abnormal

Lipid profile

TG: HDL: LDL:

Creatinine Urine microalbumin Urine protein Fundoscopy Examination of feet ECG

* Estimate/presumed: If date not known, enter 30/06/yyyy and mark the box.

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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.

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