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Cardiovascular DiseaseIn Women

QUALITY IN PRACTICE COMMITTEE

AUTHORS

Dr Naoimh KennyDr Ails n Rain


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Key to Levels of Evidence and Grades of Recommendations (1)

Levels of Evidence

Ia Evidence obtained from meta-analysis of randomised controlled trials

Ib Evidence obtained from at least one randomised controlled trialIIa Evidence obtained from at least one well designed controlled study without randomisationIIb Evidence obtained from at least one other type of well designed quasi-experimental studyIII Evidence obtained from well designed non-experimental descriptive studies, such as comparative

studies, correlation studies and case studies.IV Evidence obtained from expert committee reports or opinions and-or clinical experiences of

respected authorities

Grades of Recommendations

A Requires at least one randomised controlled trial as part of a body of literature of overall good qualityand consistency addressing the specific recommendation. (Evidence levels Ia, Ib)

B Requires the availability of well conducted clinical studies but no randomised clinical trials on the topicof recommendation. (Evidence levels IIa, IIb, III)

C Requires evidence obtained from expert committee reports or opinions and/or clinical experience ofrespected authorities. Indicates an absence of directly applicable clinical studies of good quality.(Evidence level IV)

Scottish Intercollegiate Guidelines Network 97 (www.sign.ac.uk).

Note on the use of the term Cardiovascular Disease:

Throughout this document the term Cardiovascular Disease (CVD) implies ischaemic coronary heart diseaseand its sequelae. While diseases such as e.g. dysrhythmia and heart failure may be caused by ischaemic heartdisease, and related morbidities such as stroke and peripheral arterial disease are closely related, theseconditions are not the primary focus of this document. In dealing with non-ischaemic CVD practitioners shouldrefer to other texts.

Published May 2007, ICGP 2007


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Table of Contents

I. Introduction 2

1.1 Background

1.2 Aims of the Document

1.3 Evidence-Based Medicine

II. Cardiovascular Risk Assessment 4

2.1 Identifying Target Population

2.2 Risk Factors

Non-Modifiable

Modifiable

Other Factors

2.3 Establishing Total Cardiovascular Risk

III. Clinical Presentation of CVD in Women 9

3.1 Chest Pain in Women

3.2 Myocardial Infarction

3.3 Sudden Coronary Death

IV. Investigations 10

4.1 Laboratory Investigations

4.2 Other Investigations

4.3 Resting 12-Lead ECG

4.4 Exercise Stress Testing (EST)

V. Risk Modification 11

VI. Appendices 14

Appendix 1 SC RE chart Risk Evaluation System in Primary PreventionAppendix 2 European (2003) Guidelines on Blood Pressure ManagementAppendix 3 European (2003) Guidelines on Lipid ManagementAppendix 4 Patient Information Leaflets

References 20

Acknowledgements 23

1Published May 2007, ICGP 2007


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I. Introduction

1.1 Background

Cardiovascular disease (CVD) is the leading cause of mortality in men and women on a global basis. CVDaffects men and women equally but evidence suggests that it is neither diagnosed as readily, nor treated aseffectively, in women.

In Ireland between 2001 and 2005, an average of 2,484 women died each year from ischaemic heart disease(including myocardial infarction (MI)). (2) Yet, women seem largely unaware of their risk of developingcardiovascular disease, retaining the perception that CVD is predominantly a mans disease. The pattern inwhich women suffer from CVD differs to that of men. Women delay in presenting for care of symptoms whichthey dont attribute to CVD, and indeed are less likely to present for primary preventative care from theirphysician. This perception that women are not at risk of CVD may be fuelled by the healthcare profession:physicians are slower to commence preventative therapies, and less likely to investigate women for risk factors,diagnose acute cardiac conditions, refer for specialist opinion and provide acute care for conditions such asmyocardial infarction, in women. (3,4)

At age 40 years a woman has a 31.7% lifetime risk of developing coronary heart disease (compared with 48.6%in a man). (5) Women lag behind men with their first manifestation of CVD by about 10 years, but they are

more likely than men to die after MI (6), coronary artery bypass graft and coronary angioplasty.

Fewer women enrol in cardiac rehabilitation courses compared with men, and are more likely to drop out beforecompletion. Heartwatch, a secondary prevention strategy/programme for CVD based in primary care settings inIreland, clearly illustrates this data has shown that for the first years of the programme only 24% ofparticipants have been female.

Much of the available data on patterns of CVD is taken from studies on men; in the past female subjects wereactively excluded from randomised controlled trials and so assumptions about symptoms, for example, of heartdisease in women, were basically made by extrapolating information on presentation of heart disease in men.There is evidence, however, that modes of presentation differ significantly in women compared with men.Classic chest pain, for example, is not present in all women with angina pectoris. (7)

Society and media campaigns may cause women to focus predominantly on wider-known, but less prevalentconditions, such as breast cancer. In 2005, 678 women died from breast cancer in Ireland, compared with2,225 from ischaemic heart disease. (2) Approximately twice as many women die each year from CVD thanfrom all cancers combined.

The past three decades has seen a decline in age-adjusted mortality for ischaemic heart disease for both sexesin Ireland, but this decline has been relatively less for women than for men. Irish women have a high rate ofischaemic heart disease compared with their European counterparts 90 per 100,000 women, compared toEuropean (EU 15) average of 62.2 per 100,000. (8)

It is likely that trends in the prevalence of, and death rates from, cardiovascular disease in Ireland will change asa result of the recent changes in the populations ethnicity. Various ethnic groups now resident in Ireland arerepresented in significant numbers; these groups may have a native risk for CVD statistically different to that of

the indigenous Irish population, and therefore GPs need to have heightened awareness of risk of CVD amongstthese groups.

Heart disease presents a public-health burden of equal magnitude in both sexes. There has been a decline incoronary deaths, which has left in its wake survivors, largely women and the elderly, with prevalent heartdisease that are at risk of disability and recurrent events. The economical implications of these shifts areimmense. Overall, the burden of disease remains high and could be further reduced by recognition andaggressive management of those at risk.

2 Published May 2007, ICGP 2007


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I.2 Aims of the Document

This paper has been commissioned by the Womens Health Council, and has been jointly funded by theWomens Health Council and the Irish College of General Practitioners. The Womens Health Council is astatutory body which was established in 1997 to advise the Minister for Health and Children on all aspects of womenshealth. In addition to this document there is an accompanying one-page summary sheet for use in the surgery.

This document aims to highlight the impact of CVD on womens health on an individual and societal basis, andto illustrate the differences between CVD in women and men.

After reading the document you will:

assess the risk factors for CVD in women

understand the gender differences in presentation, diagnosis and outcome

accept the importance of treating women with CVD in primary care.

The document is comprised of four main sections focussing on clinical management. The first of these focuseson risk assessment in particular identifying risk factors and outlining how total cardiovascular risk should beestablished. The subsequent sections relate to presentation of CVD in women and further management optionsincluding investigations and risk modification.

Please note the qualifier on the use of the term CVD; see inside cover for detail.

1.3 Evidence-Based Medicine

Evidence-based medicine is the conscientious, explicit and judicious use of current best evidence in makingdecisions about the care of individual patients.

Throughout this document you will see levels of evidence (indicated by roman numerals, e.g. Ia), and grades ofrecommendation (indicated by alphabetical letter, e.g. A). (1)

See Inside Coverfor Table of Evidence and Recommendations.



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II. Cardiovascular Risk Assessment

2.1 Identifying Target Population

In practice it is important to identify women at risk of CVD.

Patients generally fall into two categories:

patients with established cardiovascular disease, who have a history of symptoms, signs or acardiovascular event (secondary prevention)

asymptomatic patients at moderate or high risk for cardiovascular disease (primary prevention), becauseof:

(a) multiple risk factors resulting in a 10-year risk of >5% now (or if extrapolated to age 60) for developinga fatal CVD event

(b) markedly raised levels of single risk factors:

- cholesterol >8 mmol/l,

- LDL cholesterol >6 mmol/l,- blood pressure >180/110 mmHg (9)

(c) diabetes type 2, or diabetes type 1 with microalbuminuria. (9) *

* if using SC RE chart (9) (Level III)

2.2 Risk Factors

In practice it is thus essential to establish risk factors for each individual. This is achieved by careful history-taking, examination and some minimal investigations.

Risk factors for CVD can be classified as non-modifiable, and modifiable.

Non-modifiable Modifiable

Age

Menopausal status

Family history

Socio-economic status

Race

Cigarette smoking

Hypertension

Lipid abnormalities

Diabetes mellitus

Obesity

Sedentary lifestyle



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Non-modifiable Risk Factors

Age

Risk increases with age in both men and women. The natural distribution of risk factors, particularly inwomen, changes dramatically after age 50. (10)

Menopausal

The single most specific risk factor for women is hormonal status, with the incidence rising sharply after themenopause. (11)

Family History

There is a suggestion that a positive family history of CVD is a stronger risk factor for women than it is formen (12) (Level IV). Parental history of MI < 60 years is a particularly strong risk factor for women(13)(Level IIa).

Socio-economic Factors

Low socio-economic status significantly increases risk of CVD and is often associated with the presence ofmore risk factors, e.g. higher BMI, cigarette smoking, and elevated LDL cholesterol (14) (Level III).

Race

Certain ethnic groups are at increased risk of CVD e.g. women of central Asian extraction, African-Americanwomen.

Modifiable Risk Factors

Cigarette smoking

Smoking is the major cause of CVD in young and middle-aged women, accounting for up to half of allcoronary deaths. There is a dose-response effect associated with smoking in women. A woman whosmokes less than five cigarettes per day is twice the risk of an acute MI as a non-smoker, while that risk is11 times higher for a woman who smokes more than 45 cigarettes a day (15) (Level Ib).

Women who smoke have their first MI 19 years earlier than women who do not smoke (16) (Level IV).

More than 60% of myocardial infarctions in women younger than 50 years are attributable to smoking.

Smoking also has detrimental effects in women as it lowers HDL cholesterol and oestrogen levels,increases serum fibrinogen levels, and causes earlier onset of menopause (17) (Level IV).

The overall prevalence of cigarette smoking in Ireland is 24.7%. (2006 Office of Tobacco Control www.otc.ie)

There is an almost even split between male and female smokers. Female smoking prevalence rates haveincreased in past 12 months, whereas male smoking prevalence rates have remained constant.



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Hypertension

Hypertension is an independent risk factor for CVD in both women and men, and risk increasescontinuously as blood pressure rises from levels which are within normal range. For every 20 mmHgsystolic or 10 mmHg diastolic increase in BP there is a doubling of CVD mortality.

Isolated systolic hypertension (with its higher incidence in older women) is at least as powerful a risk factoras hypertension (12) (Level IV). Additionally, hypertension is an important marker for patients with a high-risk profile (12). Reducing blood pressure with medication decreases cardiovascular morbidity and mortalityin women to the same extent as it does in men (18) (Level Ia).

Hyperlipidaemia

Lipid abnormalities are important predictors of CVD risk in women. In women, low-density lipoprotein (LDL)cholesterol and total cholesterol levels peak between 55 and 65 years about a decade later than men.Women below the age of 65 years with lipid abnormalities have increased risk of CVD, as compared withmen and women older than 65 years (19) (Level III). Elevated triglyceride levels are more common inwomen and are also a potent independent risk factor for CVD in women (20) (Level Ia).

Lowering cholesterol levels in women appears to have similar beneficial effects as in men, but data is

limited in women particularly in primary prevention (21) (Level Ia). This is especially relevant from the sixthdecade onward for women.

Diabetes Mellitus

Diabetes mellitus and hyperglycaemia are more potent risk factors for CVD in women than in men andnegate the gender differential in age of onset (22) (Level III). Patients with type 1 diabetes have increasedrisk of developing CVD over non-diabetics, but in women the risk is 3-7 times higher compared with a 2-3fold risk in men (23) (Level III).

The prevalence of type 2 diabetes is increasing in both men and women. All patients with type 2 diabetes,regardless of renal status, are at increased risk of CVD. Mortality from MI is significantly higher in diabeticwomen than in non-diabetic women or men with or without diabetes (23) (Level III).

Obesity

There is a direct positive association between obesity and the risk of CVD in women (17).Those with BMI >

29 are three times more likely to develop CVD than lean individuals (17) (Level IV). Truncal obesity confersa higher risk than peripheral body fat distribution(24) (Level IIa). Increased waist-hip ratio and waistcircumference are highly correlated to the risk of CVD, with waist measurements > 88cm in women bearingsignificance.

Metabolic risk factors tend to cluster in obese patients:

- insulin resistance- glucose intolerance

-low high-density lipoprotein (HDL)

- small LDL particles- high triglycerides- hypertension.

This represents the metabolic syndrome and it is more prevalent in women with CVD than in men (25)(Level IIa).



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Sedentary Lifestyle

Physically active women have a significant reduction in CVD risk as compared with sedentary women (26)(Level Ib). Physical activity helps to combat obesity, reduces blood pressure and risk of type 2 diabetes,and confers extra protection against CVD, which is not explained by reduction in BMI alone. The risk of MIhas been shown to reduce by half for women if they were to walk for 30-45 minutes, three times weekly (27)(Level Ib).

Other Factors

The following are topical and relevant factors pertaining to estimation of cardiovascular risk in both women andmen. Although GPs may chart a patients readings as part of risk calculation, at the present time there isinsufficient evidence to categorically recommend implementing treatment based on these factors, whilst aimingfor reduction in cardiovascular disease. Further research in these areas may provide practitioners with betterevidence-based information regarding each of these topics.

Homocysteine

Elevated serum homocysteine levels appear to increase coronary risk both for women and men. It is amodest independent predictor of CVD in healthy populations, but there is insufficient evidence in womenregarding effects of treatment to advocate actively lowering homocysteine levels (28) (Level IV).

C-Reactive Protein

C-reactive protein (hs-CRP) is measured using a sensitive laboratory assay on serum CRP, and increasedlevels in women are associated with greater risk of cardiovascular events (29) (Level III). Although it is asensitive indicator, it is a non-specific one, and results of interventions to reduce CRP levels in women arenot known. Furthermore, screening of hs-CRP levels is not currently available at many hospital-basedlaboratories in Ireland.

Estimated GFR

There is good evidence that kidney disease (not yet kidney failure) is strongly associated with CVD and isincreasingly thought to be a risk factor for it. Decreased renal function (even before microalbuminuria) canbe detected using estimated glomerular filtration rate (eGFR) based on serum creatinine, age, sex and race.Calculation of eGFR is complex; however, online calculators facilitate estimation once the patients serumcreatinine is known. http://www.renal.org/eGFR/eguide.html. (30)

Normal GFR is approximately 100 ml / min / 1.73m2, and lower readings may indicate early stages of

chronic kidney disease, conferring a greater risk of CVD. As well as usual measures in prevention, theseindividuals require tighter blood pressure control. (30)



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2.3 Establishing Total Cardiovascular Risk

In asymptomatic, apparently healthy subjects, whose risk factor profile has been established preventiveactions (primary prevention) should be guided in accordance with the total CVD risk. This risk is bestestablished using risk charts.

Currently in Ireland there are two such charts in common use in primary care.

(1) 10-year risk CVD Event Chart (31)

From the 2nd

Joint Task Force of European and Other Societies on coronary prevention.

Features:

published in 1998

based on the original Framingham (US) model

cites 10-year risk of a CVD event

cites 20% or more as high risk

has separate risk charts for both genders, smokers and non-smokers has a separate risk chart for use in diabetics

utilised by Heartwatch programme

is available to download from the ICGP website

(2) SC RE (Systematic Coronary Risk Evaluation) system (9)

From the 3rd

Joint Task Force of European and Other Societies on coronary prevention.

Features:

published in 2003

emphasis on European populations

two categories available: high-risk and low-risk European nations

cites 10-year risk of fatal CVD

cites 5% or more as high risk

has separate risk charts for both genders, smokers and non-smokers

has separate risk charts for total cholesterol, and Tchol:HDL ratio

NO separate risk chart for diabetes*

*For individuals with diabetes (types I and II) every risk factor combination the risk will be at least twice ashigh in men, and up to four times higher in women compared with that given by the charts.

Both risk estimation systems are valid. For the purposes of this document the SC RE system will be referred

to. http://www.escardio.org/NR/rdonlyres/E5DD427D-50E2-4F1F-B287-C9F24242C29A/0/guidelines_SCORE_FT_2003.pdf

See Appendix 1 for copy of chart and instructions for use. (9)



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III. Clinical Presentation of CVD in Women

3.1 Chest Pain in Women

Angina pectoris is the most common initial and subsequent presenting symptom of CVD in women (32) (LevelIb). It is more likely in women to be uncomplicated, as compared with men when it is more likely to be asymptom of evolving MI. Classic situations that provoke angina are exertion, emotional stress, cold, sexual

activity, and after a meal. It is more common in the first hours after wakening. Symptoms arising frommyocardial ischaemia in women may be difficult to diagnose because they may present atypically (the typicalsymptoms having been classically taken from studies on men), with the following:

shoulder, neck or abdominal pain

nausea

fatigue

dyspnoea

and as such, women are more likely to delay seeking medical care when their symptoms do not match theirexpectations. Women also have a higher prevalence of vasospastic angina and microvascular angina, both ofwhich are associated with atypical chest patterns (33) (Level III).

3.2 Myocardial Infarction

Women tend to have their MIs at older ages than men, with a higher case fatality rate. (34) In these, older,women, advancing age and accumulation of risk factors and co-morbidities may have contributed to theirincreased morbidity and mortality. Studies suggest that large numbers of women with atypical MI patterns(unstable angina or non-ST-elevation MI) do not have significant large vessel CVD, suggesting differingpathology (e.g. microvascular endothelial dysfunction). (35)

Younger women (< 50 yrs) have much higher mortality rates in hospital after an MI, than men. As presentingsymptoms of MI in women are different to those in men, more women than men are incorrectly diagnosed atpresentation. (6) Non-chest symptoms are common in women with MI:

women < 65 years more likely to present with unstable angina, less likely to have ST-elevation MI

women and men >65 years tend to have similar presentation patterns women >65 years are more likely to have heart failure at presentation, as compared with men.

3.3 Sudden Coronary Death

Sixty-three percent of women who die from CVD present with sudden death (36) (Level IV). Certain risk factorshave been shown to predict the risk of sudden cardiac death in women (34) (Level IIa).

In younger women who die suddenly due to CVD, smoking is the predominant risk factor.

In older women, the dominant risk factor for sudden death is elevated cholesterol (35) (Level III).

Patients presenting with any of the following symptoms or signs require referral to specialist care:

chest pain syndromes pressure, vasospastic, nocturnal pain, either stable or unstable

dyspnoea

accelerated (malignant) hypertension (BP more than 180/110 mmHg with signs of papilloedemaand/or retinal haemorrhage)(37)

suspected phaeochromocytoma (possible signs include labile or postural hypotension, headache,palpitations, pallor and diaphoresis).(37)

(Grade A)



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IV. Investigations

4.1 Laboratory Investigations

For both female and male patients, along with usual laboratory investigations (fasting lipids and blood glucose,U/E, LFT, urinalysis) add in as required:

FBC, TFT if clinical indicators (e.g. hyperlipidaemia)

Glucose tolerance test, HBA1c if dictated and/or known hyperglycaemic state

Urinary microalbumin if known diabetes.

In women owing to higher prevalence of metabolic syndrome:

Sex hormones, serum cortisol (if clinical suspicion).

4.2 Other Investigations (both genders)

BP measurement.

BMI calculation. Abdominal girth, hip measurements.

4.3 Resting 12-lead ECG

Although widely used as a diagnostic tool, ECG testing in generally considered less accurate in women than inmen (Level III); diagnostic criteria were established in predominantly male studies. Individuals with abnormalECG, or non-diagnostic ECG with symptoms, require referral for specialist opinion. (Grade B)

4.4 Exercise Stress Testing (EST)

EST has been traditionally used in both men and women to elucidate myocardial ischaemia. However it may be lessaccurate in women (38). (Level III)

In younger women with a low likelihood of CVD, EST provides higher false-positive results.

On the other hand, single-vessel coronary heart disease, which is more common in women than in men,may not be identified by routine EST.

Because of the high false positive rate, women with atypical angina and a positive EST are likely to have othertests such as:

echocardiography

nuclear imaging

before progressing to more invasive diagnostic procedures (e.g. coronary angiography).

Therefore, in the absence of angina, direct referral for EST is not recommended for women with non-specificchest symptoms as results may be misleading (Grade C).

In women who have angina or unexplained symptoms consider referral for specialist opinion (Grade C).



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V. Risk Modification

5.1 Smoking Cessation

Smoking cessation can considerably reduce the risk of CVD in both sexes, and is known to provide protection inboth primary and secondary prevention. After 2-3 years of abstinence the level or risk in ex-smokers issimilar to those who have never smoked, regardless of the amount or duration of cigarettes smoked or the age

at cessation (39). Women smoke for different reasons than men, citing stress, anger, boredom or depression asfactors. They are also more likely to use smoking as a weight-control tool, and cite weight-gain as the reasonfor relapse after quitting. Women may benefit from pharmacotherapy more than men do(40), and studiessuggest that the combination of pharmacological therapy plus counselling/support group works best for smokingcessation in women. Consideration of factors unique to women may help physicians to be more successful intreating female smokers (40). Studies involving use of brief intervention techniques to encourage smokingcessation show similar success rates for men and women (41) (Level Ia). Thus smoking cessation approachesshould be recommended to both (Grade A).

All women should be encouraged to quit smoking. Strategies that may help can be summarized into thefollowing 5 As:

A ask: systematically identify all smokers at every opportunityA assess: determine the patients degree of addiction and her readiness to cease smokingA advise: urge strongly all smokers to quitA assist: agree on a smoking cessation strategy including behavioural counselling, nicotine replacement

therapy and/or pharmacological interventionA arrange: a schedule of follow-up visits (Grade A)

NICE guideline PH1001 Smoking cessation: Quick Reference Guide. (42)(http://guidance.nice.org.uk/PHI1/quickrefguide/pdf/English/download.dspx)

5.2 Hypertension

Reduction of blood pressure provides protection against CVD in primary prevention, and is known also toprevent further morbidity and mortality in secondary prevention, even if the BP readings are normal.

The decision to commence treatment (primary prevention) in hypertensive patients without established CVDdepends on the level of BP and on assessment of total cardiovascular risk and presence or absence of targetorgan damage (Level Ia). In secondary prevention the choice of drug used is influenced by underlyingdisease. Antihypertensive drugs should not only lower blood pressure effectively. They should have afavourable safety profile and be able to reduce cardiovascular morbidity and mortality. (38)

Five classes of drugs are widely in use for treatment of women and men:

thiazide-type diuretics

beta-blockers

ACE inhibitors calcium-channel blockers

angiotensin II antagonists.

Recommendations for use of drug category in treating hypertension are outlined in NICE guideline(http://guidance.nice.org.uk/CG34/niceguidance/pdf/English/download.dspx). (37) These guidelines do notmake a gender distinction. Currently there is no evidence to suggest benefit in use of one class of drug overanother, in women as compared with men. (37) However certain classes of antihypertensive medications arenot acceptable for use in pregnancy. (Level Ia)

See Appendix 2 for flow-chart in initiating therapy. (Grade A).



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5.3 Hyperlipidaemia

Use of cholesterol-lowering medications decreases the incidence of major coronary events in both men andwomen (Level Ia). However, their usefulness in primary prevention in women is unknown owing to limited data:women were traditionally either excluded from trials, or included in small numbers. Thus the use of statins inwomen forprimary prevention is controversial: the practice of prescribing statins for women in this way isfounded on extrapolation of results in men (Level IV).

There is sufficient good evidence to support the use of statins in women forsecondary prevention.(Level Ia). Lowering cholesterol after MI reduces major coronary events by a third in women and this benefit ismaintained at older ages. This is further borne out by another study which showed that loweringcholesterol after MI in patients with average cholesterol levels reduced death or subsequent MI by 46% inwomen. (Grade A).

See Appendix 3 for recommendations on lipid lowering in women.

5.4 Exercise and Weight Management

Exercise is useful for both primary and secondary prevention of CVD in women. Physical activity may reduce

body mass, and with maintained weight loss there are improvements in blood pressure, lipid profile, andglucose handling. Physical activity also acts as a separate protective factor against CVD, with all studiesdemonstrating an inverse relationship between physical activity and cardiovascular event. Specifically exerciseshould be prescribed for women with:

BMI > 30 or

BMI > 25 with co-morbidities (e.g. hypertension).

Exercise regimes can be prescribed in primary care. Management must be tailored to each individual. Alladults should accumulate 30 minutes or more of moderate-intensity physical activity (equivalent to walkingbriskly at 3-4 miles per hour) on most days of the week (43) (Grade C).

5.5 Diabetes

Aggressive achievement and maintenance of good blood glucose control is paramount for reduction of futurecardiovascular events. A diagnosis of diabetes is considered by many to place the individual in a higher riskcategory for cardiovascular disease than their non-diabetic physiological peers, and thus treatment of theglycaemic state is considered to be secondary prevention.

All individuals with impaired glycaemic control should be treated to optimise control. (Grade A).

5.6 Aspirin

There is good evidence for the use of aspirin in secondary prevention in women it reduces subsequent MI,stroke, and death from CVD by 25% in women with established disease. (44) (Grade A).

In healthy women (primary prevention) there is no evidence that aspirin significantly protects women againstCVD (although it does provide some protection against stroke). (45,46) (Grade A)

Aspirin has been shown to have benefit in women and men with evolving MI. (34) (Grade A)



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5.7 Thrombolytic Therapies

Thrombolysis is associated with a statistically significant reduction in mortality in both women and men. (GradeA). (47)

5.8 Nitrates

There is good evidence that nitrates do not reduce the risk of CVD events in women with known CVD. (LevelIa, Grade A). Neither do nitrates lower mortality rates in women or men with acute MI.

5.9 HRT

There is good evidence that HRT regimens do not confer protection against MI or CVD (i.e. forprimaryprevention). In fact, treatment may actually increase the risk of CVD during the first year of use. (48) (Level Ib)

Studies involving HRT forsecondary prevention of heart disease have similar conclusions. Post-menopausalwomen with established coronary disease had more CVD events on HRT within the first year of treatment, butthen comparatively fewer events in years 4 and 5 (Level Ib). These results occurred despite a reduction in LDL

levels by 11%, and increase in HDL by 10%.

Thus at the present time HRT is not recommended for either primary or secondary prevention of CVD inwomen. (Grade A)

It may be appropriate, however, for women already receiving this treatment to continue it if clinically indicated(49) (Level II).

If HRT is clinically indicated for other reasons (e.g. relief of vasomotor symptoms, bone mineral densityprotection), one should discuss perceived risks of use against perceived benefit with the woman, and facilitateher informed choice in the matter. (Grade C).



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VI. Appendices

Appendix 1: SC RE Chart Risk Evaluation System in Primary Prevention (9)

Instructions:

To estimate a persons total ten-year risk of CVD death, find the table for their gender, smoking status andage. Within the table find the cell nearest to the persons systolic blood pressure (mmHg) and totalcholesterol (mmol/l)

The effect of lifetime exposure to risk factors can be seen by following the table upwards. This can be usedwhen advising younger people.

Low risk individuals should be offered advice to maintain their low risk status. Those who are at 5% risk orhigher or will reach this level in middle age should be given maximal attention.

To define a persons relative risk, compare their risk category with that of a non-smoking person of thesame age and gender, blood pressure


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Appendix 2: European (2003) Guidelines on Blood Pressure Management (9)

Initiate drug therapy promptly in those with sustained systolic blood pressure (SBP) > 180 mmHg and/ora diastolic blood pressure (DBP) > 110 mmHg regardless of total risk.

Those with high risk of developing CVD with sustained SBP of >140 mmHg and/or DBP >90 mmHgalso require drug therapy. Lower BP to < 140/90 mmHg.

Most individuals dont need drug therapy if SBP < 140 mmHg and/or DBP < 90 mmHg.

Those with a high or very high CVD risk profile and those with diabetes can benefit from reducing BPbelow the goal of 140/90 mmHg.

Choose agents which carry a favourable safety profile, lower blood pressure effectively, and reducecardiovascular morbidity and mortality.

Certain classes of agents, most notably ACE inhibitors and angiotensin II antagonists, arecontraindicated in pregnancy and lactation; consideration of this factor must be borne in mind whentreating a woman of child-bearing potential.

Further information regarding initiating drug treatment from different categories is available atNICE clinical guidelines (http://guidance.nice.org.uk/CG34/niceguidance/pdf/English/download.dspx)Hypertension: management of hypertension in adults in primary care. (37)



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Appendix 3 European (2003) Guidelines on Lipid Management (9)

diet and exercise should be the cornerstone of serum lipid management (Grade C) if after 3-6 months, there is failure to reduce either/both total cholesterol to 1.7 mmol/l mark increased risk) (Grade B)



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Appendix 4 Patient Information Leaflets

Listed are some examples of patient information leaflets which are accessible at the online addressesprovided. They may be utilised according to the needs of your patient.

Heart Disease and Heart Attacks: What Women Need to Know. Family Doctor (USA) 2006 (50)

http://familydoctor.org/online/famdocen/home/common/heartdisease/risk/287.html

Coronary Heart Disease. Prodigy, NHS. 2007 (51)http://www.cks.library.nhs.uk/patient_information_leaflet/Coronary_heart_disease



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Acknowledgments

The authors acknowledge Ms. Aoife OBrien and Dr. Sarah Callanan, of the Womens Health Council,

for their assistance and support with the production of this document. At the ICGP, thanks are due to

Dr. Margaret ORiordan and the Quality in Practice committee for their helpful guidance, and to

Ms. Gillian Doran and Ms Patricia Patton for their assistance with references. Particular thanks are

due to Ms. Yvette Dalton for her work on the formatting, editing and production of the document.

***********



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