Down syndrome (DS) is associated with a high risk of stroke, as revealed by a population-level matched cohort study. The study found that individuals with DS had a greater risk of incident cerebrovascular events, especially ischemic and hemorrhagic strokes, compared to those without DS. This risk was present across all age groups and was generally higher in females. The high risk of stroke in DS individuals may be attributed to congenital heart disease, cardiac arrhythmia, and Moyamoya disease, which are more prevalent in this population.
What You'll Learn
- Congenital heart disease in Down syndrome patients can cause cardioembolic infarcts, leading to haemorrhagic stroke
- Moyamoya syndrome in Down syndrome patients can result in intracerebral haemorrhage
- Down syndrome patients with stroke have a high risk of in-hospital mortality
- Down syndrome is associated with a high risk of stroke across all age groups, especially in females
- The risk of ischemic stroke in Down syndrome patients is influenced by cardioembolic risk factors
Congenital heart disease in Down syndrome patients can cause cardioembolic infarcts, leading to haemorrhagic stroke
Congenital Heart Disease in Down Syndrome Patients
Congenital heart disease (CHD) is a common condition affecting individuals with Down syndrome, with approximately 50% of infants with Down syndrome presenting some form of heart condition. The most prevalent types of CHD in this population include atrioventricular septal defect (AVSD), ventricular septal defect (VSD), and atrial septal defect (ASD). These defects involve holes or abnormalities in the walls separating the heart chambers. The high prevalence of CHD in Down syndrome is well-documented, but the underlying reasons are not yet fully understood.
Atrioventricular Septal Defect (AVSD)
AVSD is the most frequently diagnosed heart condition in children with Down syndrome, affecting 30-47% of this population according to various studies. It is characterised by holes between the upper or lower chambers of the heart (atria and ventricles, respectively). AVSD often requires surgery, with a reported near-100% survival rate for these procedures.
Ventricular Septal Defect (VSD) and Atrial Septal Defect (ASD)
VSD and ASD are also common in individuals with Down syndrome. VSD affects the lower chambers of the heart, while ASD impacts the upper chambers. These defects are caused by holes in the walls separating the chambers.
Patent Ductus Arteriosus (PDA)
PDA is another heart condition that occurs in 5-18% of children with Down syndrome. It happens when a channel called the ductus arteriosus, which connects the fetus' heart and lungs in the womb, fails to close after birth. Symptoms may include tiredness, sweating, rapid or heavy breathing, loss of appetite, and failure to gain weight. Treatment options include watchful waiting, medications, surgery, or a transcatheter device closure procedure.
Tetralogy of Fallot
Tetralogy of Fallot is a rare heart defect, affecting approximately 0.04% of all live births. However, it is more prevalent in infants with Down syndrome, accounting for 2-6% of CHDs in this population. It involves four different heart problems: a ventricular septal defect, a narrow or obstructed pulmonary valve, an enlarged aorta, and a thicker-than-normal right ventricle. These abnormalities result in reduced blood oxygen levels in the body. Tetralogy of Fallot typically requires open-heart surgery and may require additional surgeries as the child grows.
Early Detection and Treatment
Given the high prevalence of CHDs in babies with Down syndrome, early detection and treatment are crucial. Cardiac issues can often be diagnosed during pregnancy or shortly after birth, and prompt medical intervention can improve an infant's chances of survival and long-term health. The American Academy of Pediatrics recommends that all babies born with Down syndrome be evaluated by a paediatric cardiologist within the first month of life, even if prenatal tests and general paediatric examinations did not indicate any heart defects.
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Moyamoya syndrome in Down syndrome patients can result in intracerebral haemorrhage
Moyamoya syndrome is a rare chronic cerebrovascular disease that causes stenosis of the distal portion of the internal carotid artery. Moyamoya is more common in people with Down syndrome than in the general population. The disease is characterised by progressive stenosis of the terminal portion of the internal carotid artery and its main branches, along with the development of compensatory collateral vessels at the base of the brain. This creates a haemodynamic compromise, mostly in the anterior cerebral circulation, favouring ischaemic episodes.
The collateral vessels that develop in Moyamoya syndrome are dilated perforating arteries that tend to have evidence of stress related to increased blood flow. This combination of stenosis with a network of weakened collateral vessels puts individuals at a very high risk of both ischaemic and haemorrhagic cerebrovascular events. Moyamoya disease is, in fact, a possible aetiology of intracerebral haemorrhage in people with Down syndrome.
Intracerebral haemorrhage (ICH) is the main clinical consequence of vascular amyloidosis, which is associated with Down syndrome. People with Down syndrome are at an increased risk of ICH compared to the euploid population, although it is less common than in people with duplication of the amyloid precursor protein region on chromosome 21 (dup-APP). This suggests that there may be protective mechanisms in people with Down syndrome that are not present in those with dup-APP.
The prevalence of ICH in people with Down syndrome is estimated to be 3.3% to 3.8%. However, the true age-related prevalence of ICH in this population is not yet known and further epidemiological studies are needed.
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Down syndrome patients with stroke have a high risk of in-hospital mortality
Down syndrome patients who experience a stroke seem to have a high risk of in-hospital mortality. This is especially true for female patients and those aged 50 or younger.
Risk Factors
Down syndrome patients are at a heightened risk of experiencing a stroke. This risk is present across all age groups but is generally higher for females. Several factors contribute to this increased risk:
- Cardioembolic risk: Congenital heart disease, cardiac arrhythmia, and pulmonary hypertension are more common in people with Down syndrome and are associated with a greater risk of cardiogenic embolism, a major cause of ischemic strokes.
- Hemorrhagic stroke risk: The higher risk of hemorrhagic stroke in Down syndrome patients may be due to cardioembolic infarcts undergoing hemorrhagic transformation or the use of anticoagulants in patients with congenital heart disease and arrhythmia.
- Atherosclerotic risk: While traditional atherosclerotic risk factors (except smoking) are more prevalent in Down syndrome patients under 18, these differences are small, and the association between Down syndrome and ischemic stroke appears to be independent of these factors.
Comorbidities
In addition to congenital heart disease, cardiac arrhythmia, and pulmonary hypertension, other comorbidities are more common in Down syndrome patients and may contribute to their overall risk of experiencing a stroke:
- Dementia: The prevalence of dementia is significantly greater in Down syndrome patients, especially in those aged over 50 but also present in the 19-50 age group.
- Diabetes: Diabetes mellitus is more prevalent in Down syndrome patients aged 50 or younger.
- Hypertension: Hypertension is more common in Down syndrome patients aged 19-50 but less prevalent in those over 50.
- Sleep apnea: Sleep apnea is more prevalent in Down syndrome patients aged 50 or younger.
Implications for Healthcare Planning
The high risk of stroke in Down syndrome patients underscores the need for preventative measures and specialized care to address aging-related disorders as life expectancy continues to increase for this population.
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Down syndrome is associated with a high risk of stroke across all age groups, especially in females
Down syndrome is associated with a heightened risk of stroke across all age groups, with females being at a particularly elevated risk. This is supported by a population-level matched cohort study that found that patients with Down syndrome were at a higher risk of cerebrovascular events, including ischemic and hemorrhagic strokes, compared to those without the condition. The study also revealed a higher prevalence of congenital heart disease, cardiac arrhythmia, dementia, pulmonary hypertension, diabetes, and sleep apnea in individuals with Down syndrome.
The risk of ischemic stroke in individuals with Down syndrome appears to be driven primarily by cardioembolic risk factors, including congenital heart disease, cardiac arrhythmia, and Moyamoya disease. These conditions increase the likelihood of blood clots forming and travelling to the brain, resulting in a stroke. Additionally, cardioembolic infarcts may undergo hemorrhagic transformation, contributing to the elevated risk of hemorrhagic stroke in this population.
Furthermore, individuals with Down syndrome who are aged 50 years or younger are also at an increased risk of cerebrovascular events. This finding underscores the importance of considering Down syndrome as a risk factor for stroke, regardless of age.
While the study did not find a direct causal link between Down syndrome and stroke, the association between the two conditions is significant and warrants further investigation. Understanding the underlying mechanisms and risk factors can help inform healthcare planning and improve outcomes for individuals with Down syndrome who are at risk of experiencing a stroke.
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The risk of ischemic stroke in Down syndrome patients is influenced by cardioembolic risk factors
Down syndrome (DS) is a rare chromosomal disorder that has seen increased life expectancy due to improved medical care over the past five decades, with the average lifespan increasing from 12 years to approximately 60 years. With this increased survival into late adulthood, there is a greater need to understand the medical care required by people with DS to prevent and treat aging-related disorders. While acquired cardiovascular diseases such as stroke and coronary heart disease are common in the wider population with increasing age, the risks of these diseases in people with DS were previously unknown.
A population-level matched cohort study was conducted to compare the risk of incident cardiovascular events between hospitalized patients with and without DS, adjusting for sex and vascular risk factors. The study sample was derived from hospitalization data within the Australian state of Victoria from 1993 to 2010. For each DS admission, four exact age-matched non-DS admissions were randomly selected to form the comparison cohort. The study found that DS was associated with a higher risk of incident cerebrovascular events, especially among females and patients aged 50 years or younger.
Further analysis revealed that the association of DS with ischemic strokes was substantially attenuated when adjusted for cardioembolic risk, but unaffected by adjustment for atherosclerotic risk. This suggests that the risk of ischemic stroke in DS patients is influenced by cardioembolic risk factors such as congenital heart disease, cardiac arrhythmia, and pulmonary hypertension. The study also found that DS was associated with a reduced risk of any coronary event in males but not in females.
In conclusion, DS is associated with a high risk of stroke across all ages, and this risk appears to be driven primarily by cardioembolic factors. The reasons for the increased risk of hemorrhagic stroke in DS, as well as the lower risk of coronary events in males with DS, remain unexplained and require further study.
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Frequently asked questions
People with Down syndrome are at a high risk of suffering a stroke, with a risk ratio of 2.70. This risk is expressed across all age groups and is generally higher in females than males.
The risk of both ischemic and hemorrhagic strokes is increased in people with Down syndrome. The former appears to be driven by cardioembolic risk, while the reasons for the latter are less clear.
Adult patients with Down syndrome who suffer a stroke appear to have a high intra-hospital mortality rate.
Congenital heart disease, cardiac arrhythmia, and Moyamoya disease are all associated with an increased risk of stroke in people with Down syndrome.
People with Down syndrome are also at a higher risk of developing dementia, diabetes, pulmonary hypertension, and sleep apnea, all of which may contribute to their increased risk of stroke.