Epidemiology
Stroke is a major health concern worldwide. It accounts for 11% of all deaths in England and Wales.[9] Each year in England 2000 people have a first episode of TIA. The age-adjusted annual incidence rate for TIA in the UK has been estimated at 190 cases per 100,000 population.[10] This is slightly higher than the reported incidence in Spain (35-60/100,000) and Belgium (68 to 102 /100,000).[11][12] The exact number of TIAs is difficult to establish with certainty due to the potential for a transient neurological deficit to be caused by the many conditions that mimic true cerebral ischaemia, and because a large number of TIAs go unrecognised. Approximately half never come to medical attention.[13]
Risk factors
In patients with atrial fibrillation without valvular disease, the relative risk for TIA is 2.5- to 5-fold higher than in patients without atrial fibrillation. There is a dramatically higher risk when associated with valve abnormality.[17][19]
Persistent atrial fibrillation appears to have a higher risk than intermittent fibrillation.[19]
Atrial fibrillation causes stasis in the left atrium, which increases the chance of thrombus formation in the left atrial appendage. Thrombus once formed inside the heart can embolise, creating TIA or stroke.
Odds ratio of 2.0 for TIA. Aortic valve disease has higher risk than mitral valve disease.[19]
The mechanism of association is likely to be due to valve abnormality forming a thrombogenic focus in the heart and thus predisposing to embolic events.
Strong for high-grade stenosis. Risk of stroke, TIA, or death in asymptomatic stenosis ranges from 11% to 21% with medical management only.[20] Higher rates of stenosis (>70%) are associated with significantly increased risk compared with moderate stenosis (50% to 69%).
Symptomatic intracranial atherosclerotic arterial stenosis is one of the most common causes of stroke worldwide and is associated with a high risk of recurrent stroke.[21] Large artery intracranial occlusive disease affecting the middle cerebral artery, the intracranial portion of the internal carotid artery, the vertebrobasilar artery, and the posterior and anterior cerebral arteries is more common in Asian patients.[22]
This may be due either to stasis, leading to increased risk of cardioembolic events, or via common risk factors for cerebrovascular disease and ischaemic heart failure. The odds ratio for congestive heart failure and TIA is 2.4.[19]
The most common risk factor for cerebrovascular disease.
Relative risk for TIA is approximately 2- to 5-fold in the presence of hypertension.[17][19] The higher the chronic BP elevation, the more this risk factor is important for cerebral ischaemia, forming a continuous risk association.
Mechanism is via increasing likelihood of atherosclerotic vascular disease.
There is a direct relationship between elevated total cholesterol and low-density lipoprotein cholesterol (LDL-C) and increased risk of ischaemic stroke. Relationship of other lipid profile components and stroke is more complex. Primary stroke prevention trials show 11% to 40% reduction in stroke risk with statin therapy.[23]
Diabetes is a potent risk factor for atherosclerotic disease and has been reported to be present in up to one third of patients who present with cerebral ischaemia.[24][25] The presence of diabetes increases the risk for TIA by an odds ratio of 1.5 to 2.[17][19][26]
Diabetes is frequently associated with other atherosclerotic risk factors in the metabolic syndrome. It is recommended that the patient with diabetes be recognised to be at greater than average risk for cerebrovascular disease. As a result, patients with diabetes are felt to merit aggressive management of other modifiable risk factors.
Tobacco abuse is one of the most important modifiable risk factors for cerebrovascular disease, and smokers have 1.5 to 2 times the risk of non-smokers for cerebrovascular events.[17][27]
Tobacco smoke may increase blood viscosity and increase coagulability.
The increased risk wanes with smoking cessation, but some increased risk remains, likely associated with lasting atherosclerotic vascular changes.
The association between smoking and ischaemic stroke is strongest in younger patients.[27]
Alcohol misuse is strongly associated with increased risk for stroke.[28] The association varies by pattern of consumption, with increased risk in heavy episodic ('binge') drinking (odds ratio [OR] 1.39) and heavy alcohol use (OR 1.57). Geographic region also plays a role, with low levels of alcohol consumption associated with reduced risk of stroke in Western Europe and North America only (OR 0.66).[29] Alcohol consumption is associated with elevated blood pressure, and increases the risk of other cardiovascular disease.[30]
TIAs are more common in middle age and in older people.[1] Symptoms in a young patient increase the possibility of alternative diagnosis or a less common aetiology for ischaemia, such as congenital heart disease, paradoxical emboli, drug use, or hypercoagulability.
In selected cases, such as the young TIA patient with a PFO, atrial septal aneurysm, and significant shunt, there may be an association with stroke.[31] For the unselected general population, the presence of a PFO does not significantly increase the risk of cerebral ischaemia. The relationship between PFO and TIA is complicated by the commonness of PFO in the population, and a clear causal relationship has not been established: it is estimated that approximately 25% of the population has a PFO, but in 80% of patients with PFO and stroke the PFO is incidental.[32][33] However, in patients with cryptogenic stroke, closure of PFOs has been shown to reduce recurrent stroke rates.[34]
It appears that vigorous physical activity may be protective against later cerebrovascular events.[35] Data from a large prospective study demonstrate that moderate to vigorous exercise four times per week may be protective against stroke, and show a possible association between self-reported physical inactivity and stroke.[36]
Obesity, particularly abdominal obesity, is weakly associated with cerebrovascular disease. In population studies, obesity has been shown to increase risk for ischaemic stroke by 50% to 100% compared with patients who have a normal weight.[28] The causal pathway from obesity to stroke risk is mediated by factors that track closely with weight, particularly elevated blood pressure, atrial fibrillation, dyslipidaemia, and hyperglycaemia.[28][37]
The majority of TIAs occur in patients who lack any hypercoagulability, with only 1% to 4.8% of strokes being due to coagulation disorders.[8]
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