Epidemiology

There are more than 100,000 strokes in the UK each year causing 38,000 deaths, making it a leading cause of death and disability.[5][6][7] People are most likely to have a stroke over the age of 55.[8][7] Stroke is the third leading cause of death and a major cause of disability in the US, and the third leading cause of death in Canada.[9][10] Ischaemic stroke prevalence can be further sub-divided according to pathophysiological mechanism: extracranial atherosclerosis (10%), intracranial atherosclerosis (10%), cardioembolic (25%), lacunar infarction ([small vessel disease] 15%), indeterminate aetiology ([i.e., cryptogenic] 30%), or other defined causes (10%). Ischaemic stroke is more common in older people, people with lower levels of education, and African-American or Hispanic people.[11] The overall incidence of stroke as well as stroke mortality has been decreasing over the last few decades; this is thought to be driven by improvements in stroke care.[12]

Risk factors

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older age

Even after controlling for other age-related conditions such as hypertension, this remains a strong non-modifiable risk factor.[11]

family history of stroke

Stroke-causing genetic disorders with mendelian inheritance are rare. However, twin studies show that a significant portion of stroke risk is heritable, and epidemiological studies show that family history of stroke is a risk factor.[14]

Numerous candidate genes have been proposed, but none have yet been consistently replicated as a strong risk factor for stroke.[15]

history of ischaemic stroke

History of previous ischaemic stroke indicates that the patient may sustain more ischaemic strokes in the future (particularly if risk factors, e.g., hypertension, are not corrected).

hypertension

Strongly associated with increased incidence of ischaemic stroke.[16]

smoking

Strongly associated with increased incidence of ischaemic stroke.[17]

diabetes mellitus

Strongly associated with increased incidence of ischaemic stroke.[18]

atrial fibrillation

Strongly implicated in the risk of cardioembolic stroke but not other ischaemic stroke sub-types.[19]

comorbid cardiac conditions

Several other cardiac conditions have been reported as potential causes of cardioembolism, with varying degrees of evidence. These conditions include myocardial infarction with regional wall motion abnormalities or decreased left ventricular ejection fraction, valvular disease, patent foramen ovale with or without atrial septal aneurysm, mitral valve prolapse, prosthetic heart valve, and cardiomyopathy.[20]

carotid artery stenosis

Modestly associated with risk of first ever ipsilateral ischaemic stroke and strongly associated with stroke recurrence after ipsilateral ischaemic stroke.[21][22]

Degree of stenosis is related to the risk of recurrent stroke.[23]

sickle cell disease

Associated with vascular stenosis, brain ischaemia, and Moyamoya disease (vascular occlusion affecting circle of Willis). In children, prophylactic transfusion based on transcranial Doppler ultrasound criteria has been shown to lower subsequent stroke risk.[24]

dyslipidaemia

Large prospective studies have shown that increased serum total cholesterol is modestly associated with an increased risk of ischaemic stroke.[25]

There are few studies on the association of low-density lipoprotein cholesterol with stroke, and the results are conflicting.[20] A meta-analysis showed that increased high-density lipoprotein is protective against ischaemic stroke.[26]

lower levels of education

Stroke symptoms are more likely among those with lower income and lower educational attainment.[11]

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African-American or Hispanic ancestry

Have been associated with increased incidence of ischaemic stroke.[11][27][28] Some, but not all, of this increased risk is accounted for by higher prevalence of known vascular risk factors such as hypertension and diabetes.

poor diet and nutrition

Epidemiological studies show a relationship between decreased stroke risk and increased consumption of fruits and vegetables,[29] decreased consumption of sodium,[30] and increased consumption of potassium.[31]

The effects of decreased sodium and increased potassium intake may be mediated by a lower risk of hypertension.

physical inactivity

Decreased physical activity has been associated with increased risk of ischaemic stroke.[32]

obesity

Overweight and obese people have a modestly increased risk of ischaemic stroke.[33][34]

alcohol abuse

Heavy alcohol use is associated with an increased risk of ischaemic stroke.[35]

Light to moderate alcohol consumption may be protective against ischaemic stroke.[35]

oestrogen-containing therapy

A small increased risk of ischaemic stroke may be present in users of oral contraceptive pills; however, studies are conflicting.[36]

Clinical trials of oestrogen or oestrogen plus progestogen in post-menopausal women have shown an increased incidence of ischaemic stroke.[37][38]

illicit drug use

Several drugs may influence stroke risk. Cocaine and other drugs may cause changes in blood pressure or vasculitic-type changes in the intracranial circulation.

Unsafe intravenous injections may lead to infective endocarditis with subsequent cardioembolism, or paradoxical embolism of injected foreign material.

migraine

Case-control studies show an elevated risk of stroke associated with migraine, particularly in younger women and in those with migraine with aura.[39]

hyperhomocysteinaemia

Prospective and case-control studies show that higher serum homocysteine levels are associated with a higher risk of ischaemic stroke. However, a randomised trial of homocysteine lowering to prevent stroke showed no benefit of therapy.[40] Subsequent studies with stroke as a secondary endpoint have shown varying results.[41][42] Therefore, although homocysteine is clearly a marker of ischaemic stroke risk, it remains unclear whether homocysteine itself causes stroke.

elevated lipoprotein(a)

Most studies of lipoprotein(a) and ischaemic stroke show increased risk with higher lipoprotein(a) levels. Lipoprotein(a) levels can be lowered with niacin, but it is not known whether lipoprotein(a) reduction reduces the risk of ischaemic stroke.

hypercoagulable states

Elevated anti-cardiolipin or anti-beta2-glycoprotein-1 antibody levels have been associated with stroke.

Hereditary conditions associated with venous thromboembolism (e.g., antithrombin III deficiency, protein C deficiency, protein S deficiency, factor V Leiden mutation, or prothrombin gene mutations) have not been found to be risk factors for ischaemic stroke[20] but are related to the risk of cerebral venous sinus thrombosis.

The possibility that hypercoagulable states may be more strongly associated with certain stroke sub-groups, including stroke in young people, is plausible but has not been evaluated in large studies.

elevated C-reactive protein

Associated with an increased risk of stroke after controlling for other risk factors.[43] Whether it directly causes stroke or is merely a marker of risk is uncertain.

aortic arch plaques

Aortic arch plaques may be a risk factor for recurrent stroke and death. In cases of cryptogenic strokes, further diagnostic tests are warranted to search for large aortic plaques.[44]

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