Hot Topic No.25.
Coronary Heart Disease.
•	The presentation of CHD is one of the most important tasks for General Practice.
•	CHD remains the principal cause of death in the UK,  and 1/5 of  deaths occur below age 65yrs.
•	The main risk factors are:
•	Hypertension
•	Hypercholesterolaemia
•	Smoking/Obesity
•	Diabetes.
Coronary Heart Disease – National Service Framework;
•	Published by DOH in March 2000 – Designed to “Transform the prevention, diagnosis and treatment of CHD”.
•	More than 1.4 million people suffer from angina in the UK.
•	300,000 people have heart attacks every year.

Aims of framework:
•	Sets out a programme designed to achieve the Government target of cutting CHD and Stroke incidence by an ambitious 40% by 2010.
•	It sets 12 standards for the prevention, diagnosis and treatment of CHD.
•	Describes service models and, explains how, standards can be delivered and progress will be monitored, with milestones and goals.

What this means for GP’s:
•	By April 2001, all practices should have created a register of CHD patients and then provide structured care within nationally accepted guidelines.
•	Identify patients who are at risk of CHD and offer appropriate advice and treatment to reduce their risks.
•	Regular audits.

Who are priority patients for risk reducing interventions?
1)	Those with established CHD or other atherosclerotic disease.
2)	People at high risk of developing CHD or other atherosclerotic disease due to a combination of risk factors including:
•	Smoking.
•	Hypertension.
•	Lipids.
•	Diabetes.

3)	Close relatives of patients with early onset CHD or other atherosclerotic disease.

Coronary Risk prediction Charts:
•	In Primary prevention, estimation of coronary risk may be made using The Joint British Society’s CHD risk prediction charts.
•	Aimed to help doctors decide when risk-modifying therapy is needed in primary prevention and NOT for calculating risk in secondary prevention, as these patients are already considered to be at high risk.
•	Factors incorporated into calculation of risk include:
Patient age, sex, smoking status, systolic blood pressure, total cholesterol:HDL cholesterol ratio, and whether or not the patient has diabetes.
•	The over 30% group are the high priority patients to target for reducing CHD risk in Primary prevention.  The 15-30% risk group should then be targeted as resources permit.

Non-Modifiable Risk Factors:
•	Non-modifiable risk factors for CHD include age, sex and family history.
•	The risk for developing CHD is lower for women, but absolute risk for CHD increases with age in both genders.
•	Family history of CHD is a well-established risk factor.

Modifiable Risk Factors:
•	In both primary and secondary prevention, the role of modifiable non-pharmacological “Lifestyle changes” is of paramount importance and can produce significant risk reduction.  These include;

1)	Smoking:
•	There is a strong dose-response relationship between CHD and the duration and intensity of smoking.
•	Passive smoking can increase a non-smokers risk of heart disease by 23 to 25%.
•	Smoking cessation post-MI reduces mortality by 25-50%.
•	In patients with established CHD, the level of risk falls to that of non-smokers within 2-3 years of stopping smoking.

2)	Alcohol Consumption:
•	Most population studies have shown a J-shaped relationship between the use of alcohol and all-cause mortality, although some have observed a linear relationship.
•	A J-shaped relationship means, that those who drink moderately are at lower risk of developing CHD than those who don’t drink at all (protection around 2 units /day).  This is unrelated to the type of drink.

3)	Body Weight: BMJ 1997; Body weight:Implications for the prevention of CHD, stroke and DM in a cohort of middle-aged men.
•	Body Mass Index (kg/m2):  Obesity is a well establishes risk factor for CHD.
•	The relationship between weight and all cause mortality is J-shaped or U-shaped.
•	All cause mortality in middle- aged men is increased at a BMI < 20(largely due to cancer and non-CVD deaths), and at a BMI>30 mainly due to cardiovascular deaths.
•	Healthiest BMI of middle-aged men is around 22.
•	Obesity can also lead to an adverse lipid profile, glucose intolerance and an increase in blood pressure.  Modest reductions in weight (5-10kg in 1 year), often bring substantial benefits – Am Journal of Epidemiology, 1995.

Waist: Hip Ratio: JAMA: 1998. 
•	Body fat distribution has also been shown to be an independent risk factor for both men and women.
•	Women with a waist to hip ratio of 0.76 or higher or a waist circumference of 76.2cm(30inchs) or more, have twice as high a risk of developing CHD.
•	In men the importance of hip to waist ratio may be age related.  In younger men (<65yrs), obesity regardless of fat distribution is a stronger risk factor for CHD.
•	However, when men get older (>65yrs), the waist to hip ratio may be a better predictor of CHD risk.

Diet:
Fat: 
•	Trials have shown that diets low in saturated fat and supplemented with polyunsaturated fat reduce coronary mortality.
•	Consumption of fish at least once a week may reduce the risk of sudden cardiac death in middle-aged men with no history of CHD-(DART trial – Diet and re-infarction trial).
Salt:
•	Halving salt intake can lower blood pressure by approximately 4mmHg systolic and 2mmHg diastolic. (Meta-analysis, JAMA 1998).

Antioxidants:
•	Role relating to CHD is still inconclusive.
•	Epidemiological studies have generally reported a reduction in CHD in patients who have an increased intake of Vitamin E, C and beta-carotene.  Vitamin E shows the most promising correlation with CHD.
•	RCT’s have shown little benefit (the Chinese study/the CHAOS study HOPE study).
Management of Dyslipidaemia:
Secondary causes of raised cholesterol include – Hypothyroidism, nephrotic syndrome, DM, biliary obstruction and obesity.  High triglycerides are often secondary to excessive alcohol intake and DM.  Secondary causes should be excluded before considering drug therapy.
There are 5 main statin outcome studies;

See attached E-Mail.

•	The 4S study showed that Simvastatin significantly reduced both coronary mortality and overall mortality in patients with high cholesterol levels and a history of CHD.
•	It was uncertain as to whether benefits would be observed in individuals with mild to moderate elevations of cholesterol (who represent the majority of the population who develop CHD), until the LIPID and CARE studies were conducted.
•	Both studies showed that treatment with Pravastatin was associated with impressive reduction in coronary events.
•	The first Primary prevention trial was the WOSCOP study in which Pravastatin significantly reduced cardiovascular mortality and reduced overall mortality in middle-aged men with high cholesterol and no prior history of CHD.
•	The AFCAPS/TexCAPS study showed benefits in reducing coronary events in a similar population but with lower baseline cholesterol.  The study was insufficiently powered to show effects on mortality.

Secondary Prevention versus Primary Prevention:
Cost-Effectiveness:
•	The absolute benefit of lipid lowering is less in primary prevention than in secondary prevention because patients with established vascular disease are at greater risk of recurrent events and will benefit more from lipid-lowering therapy.
•	Reinforcing this- Three times more men has to be treated for 5 years to prevent one endpoint in WOSCOPS (Primary prevention), than in 4S (secondary prevention).
•	The first priority for lipid-lowering therapy should therefore be patients with established vascular disease.

Primary Prevention:
•	Serum cholesterol alone is a poor predictor of CHD risk.  The decision to prescribe lipid-lowering therapy in primary prevention depends on the individual’s overall CHD risk- Using Joint British Society’s risk prediction chart.
•	Priority patients are those with a 30% or more risk of developing CHD over the next 10 years.  Cut-off values - total cholesterol>5mmol/l or LDL-C>3mmol/l.

Secondary Prevention:
•	Everyone with a previous MI or angina or established atherosclerotic disease should receive statin therapy if their total cholesterol is >5mmol/l and LDL-C<3mmol/l, or a reduction of 25%, whichever is lower.  Joint British recommendations on prevention of heart disease in clinical practice, 1998.

30% Vs 15%:
•	The WOSCOP study has shown that the benefits of statin therapy are apparent in patients with a 10- year CHD risk as low as 15%.
•	The decision to treat those with 10- year risks of 15% or 30% is merely an economical one.
•	The WOSCOPS study showed that at a 30% risk, the NNT for 5 years, to prevent one cardiovascular event is around 80. 
•	 If the 30% threshold were applied across England, 3.4% of those aged 35-69 would be eligible for primary prevention with a statin.  
•	If the risk was lowered to 15%, this figure rises to 20% of the same population.

Diabetics:
•	Subgroup analyses of the statin outcome studies have shown that diabetic patients benefit from statin therapy.
•	Significant reductions in major coronary events were shown with pravastatin in the CARE study, and with Simvastatin in the 4S study.
•	Other studies with greater numbers of diabetic patients are underway using atorvastatin, cerivastatin and fenofibrate.
•	Risk predicition charts take diabetes into consideration when recommending statin therapy for primary prevention.  However,
•	Diabetics with no CHD are estimated to have as high a risk as non-diabetics with established vascular disease.  It has been argued that it may be more appropriate to treat diabetics as vigorously as patients requiring secondary prevention.

The Elderly:
•	In the 4S and CARE study, the magnitude of the reduction in risk of major coronary events was greater in the over 60’s than under 60’s.
•	None of the trials included patients over the age of 75, so no definite conclusions can be made regarding efficacy in the very elderly.
•	Mortality data from the Northern Board in N.Ireland in 1997 showed that patients over 75 represented more than 60% of the total cardiovascular deaths.
•	The N.Ireland CREST guidelines see no reason for excluding the over 75’s on age grounds alone, provided they are otherwise fit and well.

Stroke:
•	Stroke was not a pre-defined endpoint in the 4S study, but post-hoc analysis showed that Simvastatin therapy was associated with a 30% reduction in stroke.
•	Pravastatin reduced stroke by 31% in the CARE study and 19% in the LIPID study.
•	Meta-analyses of the statin trials have also observed a significant reduction in fatal and non-fatal stroke of around 30% in secondary prevention.

Secondary Prevention:
What risk factors should be managed post-MI?
•	The most important risk factors requiring active treatment are – 
•	Diabetes.
•	Hypertension
•	Hyperlipidaemia
•	Smoking cessation.
•	The 2 most important drugs for consideration post-MI are Aspirin and a -blocker.
•	ACE inhibitors will also be of benefit in those with left ventricular dysfunction or heart failure. 
•	The role of lipid- lowering drugs has already been discussed.

Aspirin:
•	The benefit of aspirin in secondary prevention of MI has been summarised in the 2 Anti-platelet Trialists’ Collaboration Studies (ATC).
•	These concluded that 150mg of aspirin should be given for one month following acute MI.
•	For long-term secondary prevention, a dose of 75mg daily is sufficient, and reduces vascular events by 29%.  Although trials lasted <4years, it is probable that the benefits last longer, and it should therefore be given indefinitely.
Contra-indications to aspirin are active peptic ulceration, haemophilia and other bleeding disorders.
•	A case control study has shown NO difference in toxicity between e/c and standard formulation aspirin in daily doses of 325mg or less.
•	It has been estimated that 75mg daily would offer a 40% lower risk than 300mg daily.

-Blockers:
Evidence for use post-MI:
•	The first key study was the Norwegian Multicentre Study, in which timolol reduced overall mortality by 39% and reinfarction by 28%.
•	Similar results have been obtained using Propanolol, Metoprolol and Acebutolol.
•	Meta-analyses have shown that long term therapy with beta-blockers post-MI reduces total mortality by around 23%, and sudden death by 50%.
•	In the UK, only 38% of patients are prescribed -blockers.
•	The ISIS-1 trial is one of a number, which showed clear benefit of giving -blockers within 24hrs post-MI.
•	Recent evidence from a systematic review and meta- regression analysis (BMJ, 1999) suggested that early administration is unlikely to be of benefit unless treatment is continued long-term.