Cardiovascular Disease: Risk Assessment and Prevention

Introduction

Cardiovascular disease (CVD) is an umbrella term for the conditions that result from atherosclerosis affecting the arterial tree. It includes coronary artery disease, cerebrovascular disease and peripheral arterial disease, and it remains responsible for around a quarter of all deaths in the UK.¹

The important idea for exams is that these are not separate diseases. They share one pathological process, one set of risk factors and largely one preventive strategy, which is why a patient presenting with intermittent claudication needs their coronary and cerebrovascular risk addressed at the same time.

Much of the clinical work in CVD happens before any symptoms appear. Identifying who is at risk, quantifying that risk, and intervening early is a core primary care skill and a common OSCE and written exam topic.

Aetiology

Atherosclerosis is a chronic inflammatory process affecting medium and large arteries. It develops over decades and is well established long before it causes symptoms.²

Plaque development

1. Endothelial dysfunction. Shear stress, smoking, hyperglycaemia and hypertension damage the endothelium, making it more permeable and more adhesive to leucocytes.
2. Lipid entry and oxidation. LDL cholesterol passes into the intima and is oxidised, which is pro-inflammatory.
3. Foam cell formation. Monocytes migrate in, become macrophages and engulf oxidised LDL, becoming lipid-laden foam cells. Aggregated foam cells form the fatty streak, visible even in adolescence.
4. Fibrous plaque. Smooth muscle cells migrate from the media and lay down a collagen cap over a necrotic lipid core, producing a mature atheromatous plaque.

Why plaques cause events

A plaque causes problems in two ways. A large, stable plaque progressively narrows the lumen and limits flow when demand rises, producing stable symptoms such as angina or claudication. A smaller plaque with a thin, inflamed cap may rupture or erode, exposing thrombogenic material and triggering acute thrombosis. This is the mechanism behind myocardial infarction and most ischaemic strokes.

This explains an initially counterintuitive point: the plaque that causes a myocardial infarction is often not the most stenotic one. Plaque stability matters as much as plaque size, which is why statins reduce events out of proportion to the change they produce in luminal diameter.

Risk factors

Risk factors are conventionally split into those that can and cannot be modified. In practice the distinction matters because it determines where the consultation goes.³

A family history of premature cardiovascular disease means a first-degree relative affected before the age of 55 in men or 65 in women. This is worth asking about explicitly, because it both raises the calculated risk and flags the possibility of an inherited lipid disorder.

Several conditions raise cardiovascular risk more than their prevalence suggests and are easy to forget: chronic kidney disease, rheumatoid arthritis and other chronic inflammatory conditions, systemic lupus erythematosus, severe mental illness, and HIV. Atypical antipsychotics and long-term corticosteroids also contribute.

Clinical features

Atherosclerosis is asymptomatic until a vessel is critically narrowed or a plaque ruptures. How it presents depends entirely on which arterial bed is involved.

Because the process is diffuse, disease in one territory should prompt you to look for it in the others. A patient with claudication has a substantially raised risk of myocardial infarction and stroke, and their long-term prognosis is usually determined by their coronary disease rather than their legs.

Clinical examination

Examination in an asymptomatic patient is often normal, but it is used to look for evidence of established disease, for signs of severe dyslipidaemia, and for contributing risk factors.

• General: BMI and waist circumference; tar staining; xanthelasma, corneal arcus and tendon xanthomata (the last strongly suggests familial hypercholesterolaemia)
• Cardiovascular: blood pressure in both arms, heart rate and rhythm, murmurs, signs of heart failure
• Peripheral vessels: all peripheral pulses, capillary refill, carotid and abdominal bruits, and an abdominal examination for an aortic aneurysm
• Feet: ulceration, hair loss, and in diabetes a full diabetic foot check including monofilament sensation

The ankle-brachial pressure index is a useful bedside measure where peripheral arterial disease is suspected. A value below 0.9 supports the diagnosis; a value above 1.3 suggests incompressible, calcified vessels, which is common in longstanding diabetes and makes the test unreliable.

Investigations

Formal risk assessment

QRISK3 is the tool recommended in the UK. It estimates the percentage risk of a first heart attack or stroke over the next 10 years, and it is validated for people aged 25 to 84 who do not already have cardiovascular disease.⁴

QRISK3 incorporates age, sex, ethnicity, postcode-based deprivation, smoking, diabetes, family history, cholesterol ratio, blood pressure and BMI, along with several conditions that older tools missed, including chronic kidney disease, atrial fibrillation, migraine, corticosteroid use, severe mental illness and systemic lupus erythematosus.

Baseline investigations

• Full lipid profile including total cholesterol, HDL, non-HDL and triglycerides. A fasting sample is not required.
• HbA1c to identify undiagnosed diabetes or prediabetes
• Renal function and eGFR, plus a urine albumin:creatinine ratio
• Liver function tests before starting a statin, and TFTs, since hypothyroidism causes a secondary dyslipidaemia that should be corrected first
• Blood pressure, confirmed with ambulatory or home readings before diagnosing hypertension
• ECG if there are symptoms or examination findings suggesting established disease

Management

Management is divided into primary prevention, in people without established disease, and secondary prevention, in people who have already had an event. Lifestyle advice is common to both and should never be omitted because a drug has been started.

Lifestyle measures

• Smoking cessation - the single most effective intervention. Offer behavioural support plus pharmacotherapy rather than advice alone.
• Diet - a Mediterranean-style pattern: more vegetables, fruit, wholegrains, oily fish and unsaturated fats; less saturated fat, salt and refined sugar
• Physical activity - at least 150 minutes of moderate intensity activity per week, plus muscle-strengthening on two days
• Weight - aim for a BMI under 25 kg/m², with a lower threshold in people of South Asian ethnicity
• Alcohol - no more than 14 units per week, spread over three or more days

Primary prevention

Offer atorvastatin 20 mg once daily to people with a QRISK3 score of 10% or more, after a discussion of the benefits and risks. NICE is explicit that a statin can also be considered below this threshold if the person's informed preference is to take one.³

A statin is also offered without calculating QRISK3 to people with chronic kidney disease, and considered for all adults with type 1 diabetes, particularly those over 40, those with diabetes of more than 10 years' duration, and those with nephropathy or other risk factors.

Aspirin is not used for primary prevention. The bleeding risk outweighs the modest reduction in events in people without established disease.

Secondary prevention

Anyone with established atherosclerotic disease should receive atorvastatin 80 mg once daily, reduced only if there are drug interactions, a high risk of adverse effects, or patient preference. Additional treatment depends on the territory involved: antiplatelet therapy in all, plus a beta-blocker and an ACE inhibitor after myocardial infarction, and referral to cardiac rehabilitation.⁶

Check liver function before starting, and again at 3 and 12 months. Recheck the full lipid profile at 2-3 months. If the target is not met despite adherence and an increased dose, add ezetimibe; specialist options beyond that include PCSK9 inhibitors, inclisiran and bempedoic acid.³

Complications

The complications of cardiovascular disease are the events it causes: myocardial infarction, heart failure secondary to ischaemic cardiomyopathy, arrhythmia including atrial fibrillation, stroke and vascular dementia, chronic limb-threatening ischaemia and amputation, and renovascular disease.

Statin therapy is generally well tolerated. Muscle symptoms are the commonest reason for discontinuation, though randomised evidence suggests most such symptoms are not attributable to the drug itself. Rhabdomyolysis is rare. There is a small increase in the incidence of new-onset diabetes, which is outweighed by the cardiovascular benefit.

Red flags

Prognosis

Cardiovascular mortality in the UK has fallen substantially over recent decades, driven by reductions in smoking, better blood pressure control, widespread statin use and improved acute care. Despite this, CVD remains one of the leading causes of death and of years lived with disability.¹

Prognosis for an individual depends on the burden of disease at diagnosis and on how completely risk factors are addressed afterwards. Statin therapy reduces major vascular events by roughly a fifth for each 1 mmol/L reduction in LDL cholesterol, and the benefit accrues year on year with continued treatment.⁷

The practical message is that adherence matters more than the choice of agent. A patient who stops their statin after six months gains very little, which is why the counselling conversation is as much a part of management as the prescription.