Cerebrovascular disease

Cerebrovascular disease can present as stroke, transient ischaemic attack or amaurosis fugax, due to vaso-occlusive disease in the cerebral circulation, usually due to emboli from carotid atheroma plaques. Diagnosis is on clinical grounds +/- imaging and managment should focus on primary and secondary prevention as much as possible.

Prevention

What are the main strategies for prevention of cerebrovascular disease?

The prevention of cerebrovascular disease is multifactorial and should include smoking cessation, blood pressure control, modification of lipids, good glycaemic control and lifestyle factors (diet, weight and exercise).

Smoking cessation

Smoking is arguably the single most important macrovascular risk factor. Patients who smoke should be encouraged and helped to stop smoking at all costs. They are much more likely to succeed if it is done with some sort of professional support and appropriate referral should be made.

Smoking cessation clinics will provide one-to-one or group support, and have expertise in the full range of smoking cessation drugs - nicotine replacement products, bupropion (Zyban) and varenicline (Champix).

Blood pressure control

IN the 1990s, the UKPDS study showed that effective antihypertensive therapy is as important as good glycaemic control in reducing macrovascular risk in T2DM.

Blood pressure targets of 140/80 in the absence of microalbuminura and 130/80 in the presence of microalbuminuria are currently recommended in the UK for T2DM, similar targets for those with T1DM would not be unreasonable.

Overzealous BP reduction carries risks of its own and the recent publication of ACCORD-BP highlighted the risks of attempting to reduce BP to less than 120/80 mm Hg in an elderly population with T2DM at increased risk of cardiovascular disease.

Lipid modification

The precise details of treatment targets are still hotly debated topics. However, there is some agreement that most people with T2DM and T1DM over the age of 40 should probably be on a statin.

Some argue that total cholesterol target should be 4 mmol/L and LDL cholesterol target should be 2 mmol/L, however, these targets are not universally accepted.

There is also some debate about the role of 'residual dyslipidaemia' in patients already on statin therapy who are not at target and whether or not these patients should receive additional fibrate therapy. There are many diabetes specialists who would actively consider fibrate therapy in a patient on maximal tolerated statin doses who still has a total cholesterol significantly above 4 mmol/L and/or a low (<1mmol/L) HDL cholesterol +/- elevated fasting triglycerides.

A convenient fibrate is fenofibrate 200 mcg od and the safety of this in combination with a statin is actually very favorable. 

Aspirin

Aspirin should probably not be used for primary prevention of cerebrovascular disease in diabetes except in obviously high-risk individuals (e.g. smokers, marked dyslipidaemia).

Glycaemic control

Good glycaemic control is an important factor in helping to prevent cerebrovascular disease but it is only part of the strategy. Smoking cessation, lipid modifications and blood pressure control are arguably equally important components.

What glycaemic targets should be applied?

The one-size-fits-all strategy of using a single HbA1c target for the whole diabetic population is a blunt approach and it is increasingly recognised that individualised targets should be set with each patient.

The fundamental challenge is that the lower the HbA1c, generally speaking the more frequent hypoglycaemia will be. Thus for a newly diagnosed patient, who is adapting well to life with diabetes and is actively engaging with education and other aspects of self management, setting a target of 6.5% (48 mmol/mol) without experiencing unacceptably frequent hypoglycaemia is a realistic aim.

However, for a 75-year-old patient with a 10-year history of T2DM and an HbA1c of 9% (75 mmol/mol), attempting reduction to 6.5% (48 mmol/mol) will probably confer no survival advantage and may even increase mortality rate as shown by the recent ADVANCE, ACCORD and VADT trials.

Other examples of groups where caution should be applied regarding zealous reduction of HbA1c include the advanced elderly (e.g. over 80-years-old, younger if significant comorbidity is present); those with frequent hypoglycaemia and hypoglycaemia unawareness; and those who have had diabetes for many decades and have developed autonomic neuropathy, gastroparesis and other comorbidity that render coping with hypoglycaemia especially difficult.

Lifestyle

Weight control, eating a diet low in saturated animal fats and exercising regularly are all effective ways to reduce the risk of macrovascular disease.

Management

Secondary prevention measures

It is essential once a patient has presented with their first manifestation of cerebrovascular disease of any description that all secondary prevention measures are vigorously pursued (smoking, cholesterol, blood pressure, aspirin and glycaemia).

Neither TIA nor amaurosis are benign symptoms, these should be taken very seriously and the patient referred for urgent investigation - and consideration of intervention - to prevent a major stroke. Some risk stratification for referral after TIA can be made by applying the ABCD squared tool.

How do I calculate the ABCD squared score?

Just do the math...

Age >60 years +1
Blood pressure >140/90 mm Hg at initial assessment +1
Clinical features Speech disturbance (no weakness) +1
Clinical features Unilateral weakness +2
Duration of symptoms 10-59 minutes +1
Duration of symptoms >60 minutes +2
Diabetes Yes +1

A score of four or more mandates referral for specialist assessment within 24 hours. 

Aspirin

All individuals with suspected TIA or stroke should receive 300 mg aspirin PO immediately. This should be continued indefinitely.

Other antiplatelet agents

In those who develop recurrent TIA on aspirin, in sinus rhythm who have no operable carotid lesion, there is some evidence to support the use of dipyrimadole in combination with aspirin. There is no evidence, however, supporting the use of the aspirin/clopidogrel combination.

Thrombolysis

Alteplase is now licensed for thrombolysis in stroke but this should only be performed in stroke units where there are protocols, expertise and experience in performing this highly specialised therapy. It is only licensed for use within three hours of onset of symptoms and in patients with a BP of less than 180/110 mm Hg.

Carotid surgery

In any individual who has had a TIA or a non(sub)-disabling stroke and there is a carotid stenosis of more than 50% by NASCET (North American Symptomatic Carotid Endarterectomy Trial) criteria (but less than total) then carotid endarterectomy should be offered.

Current UK guidelines stipulate referral within one week from onset of symptoms and surgery within two weeks. 

Acute management of hyperglycaemia in stroke patients

Current NICE guidance recommends maintaining blood glucose between 4 and 11 mmol/L by variable rate intravenous insulin infusion (sliding scale) in the immediate post stroke period.

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