Ischemic stroke is an acute symptomatic central nervous system infarction caused by interruption of cerebral blood flow, usually from thrombosis, embolism, or proximal large-vessel occlusion, leading to ischemic tissue injury and focal neurological deficits.
Ask a research question about Ischemic Stroke. OpenScientist will conduct autonomous deep research using the Disorder Mechanisms Knowledge Base and PubMed literature (typically 10-30 minutes).
Do not include personal health information in your question. Questions and results are cached in your browser's local storage.
name: Ischemic Stroke
creation_date: "2026-05-06T03:10:37Z"
updated_date: "2026-05-06T04:14:47Z"
description: >-
Ischemic stroke is an acute symptomatic central nervous system infarction
caused by interruption of cerebral blood flow, usually from thrombosis,
embolism, or proximal large-vessel occlusion, leading to ischemic tissue
injury and focal neurological deficits.
category: Complex
disease_term:
preferred_term: Ischemic stroke
term:
id: MONDO:1060198
label: ischemic stroke
parents:
- Cerebrovascular disorder
- stroke disorder
synonyms:
- Cerebral infarction
- Ischaemic stroke
- Acute ischemic stroke
prevalence:
- population: Global, all ages
notes: >-
GBD 2021 estimated about 69.9 million prevalent ischemic stroke cases
globally, with an age-standardized prevalence rate of 819.5 per 100,000.
evidence:
- reference: PMID:39157811
reference_title: "Global, regional, and national burden of ischemic stroke, 1990-2021: an analysis of data from the global burden of disease study 2021."
supports: SUPPORT
evidence_source: COMPUTATIONAL
snippet: >-
In 2021, the global burden of ischemic stroke remained substantial, with a
total of 69,944,884.8 cases
explanation: >-
GBD modeled estimates support the high global prevalence of ischemic
stroke.
pathophysiology:
- name: Cerebral arterial occlusion
description: >-
In situ thrombosis, artery-to-artery embolism, cardioembolism, or proximal
large-vessel occlusion interrupts cerebral blood flow and initiates the
ischemic cascade.
cell_types:
- preferred_term: endothelial cell
term:
id: CL:0000115
label: endothelial cell
biological_processes:
- preferred_term: blood coagulation
modifier: INCREASED
term:
id: GO:0007596
label: blood coagulation
- preferred_term: platelet aggregation
modifier: INCREASED
term:
id: GO:0070527
label: platelet aggregation
evidence:
- reference: PMID:20670828
reference_title: "The science of stroke: mechanisms in search of treatments."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
This can develop either as a consequence of thrombosis in situ or
following embolic occlusion of a cerebral blood vessel
explanation: >-
This review supports thrombosis and embolic vascular occlusion as
proximal ischemic-stroke mechanisms.
downstream:
- target: Ischemic penumbra and energy failure
description: >-
Occlusion creates a severely hypoperfused core and a potentially
salvageable penumbra with residual perfusion.
- name: Ischemic penumbra and energy failure
description: >-
Severe flow deficits rapidly deplete ATP in the ischemic core, while
residual perfusion in the surrounding penumbra allows slower active cell
death and creates a time-sensitive target for reperfusion therapy.
cell_types:
- preferred_term: neuron
term:
id: CL:0000540
label: neuron
- preferred_term: astrocyte
term:
id: CL:0000127
label: astrocyte
- preferred_term: endothelial cell
term:
id: CL:0000115
label: endothelial cell
biological_processes:
- preferred_term: response to hypoxia
modifier: INCREASED
term:
id: GO:0001666
label: response to hypoxia
- preferred_term: cell death
modifier: INCREASED
term:
id: GO:0008219
label: cell death
evidence:
- reference: PMID:21628695
reference_title: Cellular mechanisms of neurovascular damage and repair after stroke.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
In ischemic strokes, severe blood flow deficits in the core rapidly
decrease ATP levels and energy stores.
explanation: >-
This supports energy failure as an early consequence of ischemic core
hypoperfusion.
- reference: PMID:20670828
reference_title: "The science of stroke: mechanisms in search of treatments."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
The ischemic penumbra then denotes an “at risk” region that is
functionally impaired, but potentially salvageable.
explanation: >-
This supports the penumbra as an at-risk but potentially salvageable
tissue compartment.
downstream:
- target: Excitotoxic and oxidative neuronal injury
description: >-
Energy failure disrupts ionic gradients and glutamate handling,
triggering calcium overload, oxidative injury, and cell death.
- target: Neurovascular inflammation and barrier disruption
description: >-
Ischemic injury activates vascular, glial, and immune responses in the
neurovascular unit.
- name: Excitotoxic and oxidative neuronal injury
description: >-
Energy failure and impaired glutamate reuptake promote excitotoxic calcium
influx, oxidative and nitrative stress, mitochondrial dysfunction, and
apoptotic-like cell death in neurons and neighboring neurovascular cells.
cell_types:
- preferred_term: neuron
term:
id: CL:0000540
label: neuron
biological_processes:
- preferred_term: response to oxidative stress
modifier: INCREASED
term:
id: GO:0006979
label: response to oxidative stress
- preferred_term: apoptotic process
modifier: INCREASED
term:
id: GO:0006915
label: apoptotic process
evidence:
- reference: PMID:21628695
reference_title: Cellular mechanisms of neurovascular damage and repair after stroke.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
accumulated data over the past two decades have implicated excitotoxicity,
oxidative stress and in some circumstances, apoptotic-like pathways
explanation: >-
This supports excitotoxic, oxidative, and apoptotic-like injury processes
in acute stroke cell death.
- reference: PMID:28417216
reference_title: Pathogenic mechanisms following ischemic stroke.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Brain injury following stroke results from a complex series of
pathophysiological events including excitotoxicity, oxidative and nitrative
stress, inflammation, and apoptosis.
explanation: >-
This review independently supports the multi-mechanism cellular injury
cascade after ischemic stroke.
- name: Neurovascular inflammation and barrier disruption
description: >-
Ischemic injury engages endothelial cells, astrocytes, neurons, microglia,
and peripheral immune cells; inflammatory signaling, protease activation,
and matrix injury can disrupt the blood-brain barrier and amplify tissue
damage.
cell_types:
- preferred_term: endothelial cell
term:
id: CL:0000115
label: endothelial cell
- preferred_term: astrocyte
term:
id: CL:0000127
label: astrocyte
- preferred_term: microglial cell
term:
id: CL:0000129
label: microglial cell
biological_processes:
- preferred_term: inflammatory response
modifier: INCREASED
term:
id: GO:0006954
label: inflammatory response
- preferred_term: cell-cell signaling
modifier: ABNORMAL
term:
id: GO:0007267
label: cell-cell signaling
evidence:
- reference: PMID:21738161
reference_title: "The immunology of stroke: from mechanisms to translation."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Inflammatory signaling is involved in all stages of the ischemic cascade,
from the early damaging events triggered by arterial occlusion
explanation: >-
This supports inflammation as a contributor from early post-occlusion
injury through later repair.
- reference: PMID:21628695
reference_title: Cellular mechanisms of neurovascular damage and repair after stroke.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
The BBB homeostasis is remarkably dependent on endothelial-astrocyte-matrix
interactions
explanation: >-
This supports endothelial-astrocyte-matrix interactions as central to
blood-brain barrier integrity after stroke.
phenotypes:
- category: Neurological
name: Symptomatic central nervous system infarction
diagnostic: true
description: >-
Overt neurological symptoms with tissue evidence of ischemic infarction
define ischemic stroke.
phenotype_term:
preferred_term: Ischemic stroke
term:
id: HP:0002140
label: Ischemic stroke
evidence:
- reference: PMID:23652265
reference_title: "An updated definition of stroke for the 21st century: a statement for healthcare professionals from the American Heart Association/American Stroke Association."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Ischemic stroke specifically refers to central nervous system infarction
accompanied by overt symptoms
explanation: >-
This consensus definition directly supports the diagnostic phenotype.
- category: Neurological
name: Hemiparesis
description: >-
Unilateral weakness occurs when infarction affects corticospinal motor
pathways and is a common acute stroke sign.
phenotype_term:
preferred_term: Hemiparesis
term:
id: HP:0001269
label: Hemiparesis
evidence:
- reference: PMID:35204601
reference_title: "Rapid Identification of Patients Eligible for Direct Emergent Computed Tomography Angiography during Acute Ischemic Stroke: The DARE-PACE Assessment."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
secondary signs, namely hemiparesis with limb falls (P), aphasia (A),
drowsy or worse consciousness (C), and eyeball limitation
explanation: >-
This acute ischemic stroke cohort used hemiparesis with limb falls as a
stroke severity sign.
- category: Neurological
name: Aphasia
description: >-
Dominant-hemisphere ischemic stroke can impair language production or
comprehension.
phenotype_term:
preferred_term: Aphasia
term:
id: HP:0002381
label: Aphasia
evidence:
- reference: PMID:32173230
reference_title: Prevalence and Impact of Aphasia among Patients Admitted with Acute Ischemic Stroke.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Aphasia is one of the most severe symptoms in stroke patients, affecting
one-third of acute stroke patients.
explanation: >-
This national inpatient analysis supports aphasia as a major acute
ischemic stroke symptom.
- category: Neurological
name: Dysarthria
description: >-
Motor speech impairment can occur during the acute phase after ischemic
stroke.
phenotype_term:
preferred_term: Dysarthria
term:
id: HP:0001260
label: Dysarthria
evidence:
- reference: PMID:33580596
reference_title: "Dysarthria following acute ischemic stroke: Prospective evaluation of characteristics, type and severity."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
46% (70/151) of participants had dysarthria, of which half recovered
completely from their dysarthria within 1 week
explanation: >-
This prospective acute ischemic stroke study supports dysarthria as a
common acute speech phenotype.
- category: Neurological
name: Dysphagia
description: >-
Acute swallowing impairment can occur after ischemic stroke and increases
the need for early screening because of aspiration and nutrition risks.
phenotype_term:
preferred_term: Dysphagia
term:
id: HP:0002015
label: Dysphagia
evidence:
- reference: PMID:39342159
reference_title: Comorbidities associated with dysphagia after acute ischemic stroke.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Of 2054 patients with ischemic stroke, 17.2% showed dysphagia at hospital
admission.
explanation: >-
This acute ischemic stroke cohort supports dysphagia as a clinically
important swallowing phenotype.
environmental:
- name: Vascular and metabolic risk-factor burden
notes: >-
Smoking, high-sodium diet, hypertension, high LDL cholesterol, kidney
dysfunction, hyperglycemia, and high BMI are major modifiable contributors
to ischemic stroke burden.
evidence:
- reference: PMID:37197995
reference_title: "Global Burden, Risk Factor Analysis, and Prediction Study of Ischemic Stroke, 1990-2030."
supports: SUPPORT
evidence_source: COMPUTATIONAL
snippet: >-
2 behavioral factors, smoking and diet in high sodium, and 5 metabolic
factors, including high systolic blood pressure
explanation: >-
This GBD risk-factor analysis supports behavioral and metabolic
contributors to ischemic stroke burden.
treatments:
- name: Intravenous t-PA thrombolysis
description: >-
Intravenous tissue plasminogen activator can restore perfusion in eligible
early-presenting patients, improving 3-month functional outcome while
increasing symptomatic intracerebral hemorrhage risk.
treatment_term:
preferred_term: Pharmacotherapy
term:
id: NCIT:C15986
label: Pharmacotherapy
therapeutic_agent:
- preferred_term: alteplase
term:
id: NCIT:C39607
label: Alteplase
target_mechanisms:
- target: Cerebral arterial occlusion
treatment_effect: INHIBITS
description: >-
Thrombolysis aims to dissolve the occluding thrombus and restore cerebral
perfusion.
evidence:
- reference: PMID:7477192
reference_title: Tissue plasminogen activator for acute ischemic stroke.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
treatment with intravenous t-PA within three hours of the onset of ischemic
stroke improved clinical outcome at three months.
explanation: >-
This randomized trial established early IV t-PA benefit in acute ischemic
stroke.
- name: Endovascular thrombectomy
description: >-
Endovascular clot retrieval improves disability outcomes in selected
patients with acute ischemic stroke caused by proximal anterior-circulation
large-vessel occlusion.
treatment_term:
preferred_term: surgical procedure
term:
id: MAXO:0000004
label: surgical procedure
target_mechanisms:
- target: Cerebral arterial occlusion
treatment_effect: INHIBITS
description: >-
Mechanical clot retrieval removes the proximal occlusion and restores
blood flow in large-vessel ischemic stroke.
evidence:
- reference: PMID:26898852
reference_title: "Endovascular thrombectomy after large-vessel ischaemic stroke: a meta-analysis of individual patient data from five randomised trials."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Endovascular thrombectomy led to significantly reduced disability at 90
days compared with control
explanation: >-
This pooled randomized-trial analysis supports thrombectomy for selected
large-vessel ischemic stroke.
- name: Antiplatelet secondary prevention
description: >-
Antiplatelet therapy reduces recurrent ischemic events after non-cardioembolic
ischemic stroke or high-risk transient ischemic attack, with duration and
intensity balanced against bleeding risk.
treatment_term:
preferred_term: Pharmacotherapy
term:
id: NCIT:C15986
label: Pharmacotherapy
therapeutic_agent:
- preferred_term: Antiplatelet Agent
term:
id: NCIT:C1327
label: Antiplatelet Agent
target_mechanisms:
- target: Cerebral arterial occlusion
treatment_effect: MODULATES
description: >-
Platelet inhibition reduces recurrent thrombotic arterial occlusion risk
after qualifying ischemic stroke presentations.
evidence:
- reference: PMID:34024115
reference_title: "Benefits and Risks of Dual Versus Single Antiplatelet Therapy for Secondary Stroke Prevention: A Systematic Review for the 2021 Guideline for the Prevention of Stroke in Patients With Stroke and Transient Ischemic Attack."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
DAPT was more effective than SAPT for prevention of secondary ischemic
stroke when initiated early after the onset of minor stroke/high-risk
transient ischemic attack and treatment duration was <90 days.
explanation: >-
This systematic review supports antiplatelet therapy as secondary
prevention after selected ischemic stroke or high-risk TIA presentations.
- name: Anticoagulation for atrial fibrillation-associated stroke prevention
description: >-
Anticoagulation, particularly direct oral anticoagulant therapy when
appropriate, is used after ischemic stroke associated with atrial
fibrillation to reduce recurrent embolic events while managing hemorrhage
risk.
treatment_term:
preferred_term: Pharmacotherapy
term:
id: NCIT:C15986
label: Pharmacotherapy
therapeutic_agent:
- preferred_term: Anticoagulant Agent
term:
id: NCIT:C263
label: Anticoagulant Agent
target_mechanisms:
- target: Cerebral arterial occlusion
treatment_effect: MODULATES
description: >-
Anticoagulation reduces cardioembolic clot formation that can occlude
cerebral arteries in atrial fibrillation-associated ischemic stroke.
evidence:
- reference: PMID:31984228
reference_title: "Antithrombotic treatment for secondary prevention of stroke and other thromboembolic events in patients with stroke or transient ischemic attack and non-valvular atrial fibrillation: A European Stroke Organisation guideline."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
In patients with atrial fibrillation and previous stroke or transient
ischemic attack, oral anticoagulants reduce the risk of recurrence over
antiplatelets or no antithrombotic treatment.
explanation: >-
This guideline supports oral anticoagulation for secondary prevention in
atrial fibrillation-associated ischemic stroke or TIA.
- name: Primary prevention through vascular risk-factor control
description: >-
Stroke prevention focuses on cardiovascular and brain-health domains
including diet, activity, weight, sleep, glycemic control, blood pressure,
lipids, and tobacco avoidance.
treatment_term:
preferred_term: supportive care
term:
id: MAXO:0000950
label: supportive care
target_mechanisms:
- target: Cerebral arterial occlusion
treatment_effect: MODULATES
description: >-
Risk-factor control reduces the vascular conditions that promote
thrombotic and embolic stroke.
evidence:
- reference: PMID:39429201
reference_title: "2024 Guideline for the Primary Prevention of Stroke: A Guideline From the American Heart Association/American Stroke Association."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
These recommendations align with the American Heart Association's Life's
Essential 8 for optimizing cardiovascular and brain health
explanation: >-
This guideline supports multi-domain vascular risk-factor control for
primary stroke prevention.
datasets:
Ischemic stroke (IS) is brain tissue infarction due to occlusion of cerebral blood flow (thrombosis/embolism), producing acute focal neurologic deficits and major global disability and mortality burden. Contemporary evidence highlights (i) persistently high absolute global burden despite improvements in age-standardized rates, (ii) hypertension and dyslipidemia (especially high systolic blood pressure and high LDL-cholesterol) as leading modifiable contributors to disability-adjusted life-years (DALYs), and (iii) large, real-world improvements in evidence-based acute care and secondary prevention processes in organized stroke systems (e.g., Get With The Guidelines–Stroke in the US). (zhu2025globalandregional pages 1-5, liu2025globalregionaland pages 1-2, bushnell20242024guidelinefor pages 2-3, li2024globalregionaland pages 1-2, xian2024twentyyearsof pages 3-4)
| Domain | Metric | Value | Population/setting | Year(s) | Source (include DOI URL) | Notes |
|---|---|---|---|---|---|---|
| Burden | Prevalent ischemic stroke cases | 69,944,884.8 cases | Global; GBD 2021 ischemic stroke estimates | 2021 | Li et al., eClinicalMedicine (2024), https://doi.org/10.1016/j.eclinm.2024.102758 (li2024globalregionaland pages 1-2) | Absolute prevalent case count |
| Burden | Age-standardized prevalence rate (ASPR) | 819.5 per 100,000 | Global; GBD 2021 | 2021 | Li et al., eClinicalMedicine (2024), https://doi.org/10.1016/j.eclinm.2024.102758 (li2024globalregionaland pages 1-2) | 95% UI 760.3–878.7 |
| Burden | Age-standardized incidence rate (ASIR) | 92.4 per 100,000 | Global; GBD 2021 | 2021 | Li et al., eClinicalMedicine (2024), https://doi.org/10.1016/j.eclinm.2024.102758 (li2024globalregionaland pages 1-2) | 95% UI 79.8–105.8 |
| Burden | Age-standardized death rate (ASDR) | 44.2 per 100,000 | Global; GBD 2021 | 2021 | Li et al., eClinicalMedicine (2024), https://doi.org/10.1016/j.eclinm.2024.102758 (li2024globalregionaland pages 1-2) | Mortality rate |
| Burden | Age-standardized DALY rate | 837.4 per 100,000 | Global; GBD 2021 | 2021 | Li et al., eClinicalMedicine (2024), https://doi.org/10.1016/j.eclinm.2024.102758 (li2024globalregionaland pages 1-2) | 95% UI 763.7–905 |
| Prevention | Antihypertensive therapy intensity needed for BP control | ~30% controlled with a single antihypertensive; most required 2–3 medications | Randomized trial evidence summarized in AHA/ASA primary prevention guideline | Evidence summarized through 2024 | Bushnell et al., Stroke (2024), https://doi.org/10.1161/STR.0000000000000475 (bushnell20242024guidelinefor pages 2-3) | Supports guideline emphasis on aggressive BP control as a primary stroke-prevention strategy |
| Care quality | Anticoagulation for atrial fibrillation/flutter at discharge | 55.7% → 97.2% | U.S. GWTG-Stroke registry; eligible acute ischemic stroke patients | 2003 → 2022 | Xian et al., Stroke (2024), https://doi.org/10.1161/STROKEAHA.124.048174 (xian2024twentyyearsof pages 1-2, xian2024twentyyearsof pages 3-4) | Major improvement in secondary prevention quality metric |
| Care quality | Door-to-needle time ≤60 min | 19.0% → 75.3% | U.S. GWTG-Stroke registry; thrombolysis-treated acute ischemic stroke | 2003 → 2022 | Xian et al., Stroke (2024), https://doi.org/10.1161/STROKEAHA.124.048174 (xian2024twentyyearsof pages 1-2, xian2024twentyyearsof pages 3-4) | Time-to-treatment benchmark improved ~4-fold |
| Care quality | Arrive-by-3.5 h / treat-by-4.5 h | 15.2% → 92.9% | U.S. GWTG-Stroke registry; eligible early-arriving acute ischemic stroke | 2003 → 2022 | Xian et al., Stroke (2024), https://doi.org/10.1161/STROKEAHA.124.048174 (xian2024twentyyearsof pages 1-2, xian2024twentyyearsof pages 3-4) | Reflects expansion and uptake of timely IV thrombolysis workflows |
| Care quality | Smoking cessation counseling | 44.7% → 97.8% | U.S. GWTG-Stroke registry; eligible stroke/TIA patients who smoke | 2003 → 2022 | Xian et al., Stroke (2024), https://doi.org/10.1161/STROKEAHA.124.048174 (xian2024twentyyearsof pages 1-2, xian2024twentyyearsof pages 3-4) | Prevention-focused discharge quality measure |
| Care quality | Dysphagia screening | 53.8% → 83.5% | U.S. GWTG-Stroke registry; eligible acute ischemic stroke patients | 2003 → 2022 | Xian et al., Stroke (2024), https://doi.org/10.1161/STROKEAHA.124.048174 (xian2024twentyyearsof pages 1-2, xian2024twentyyearsof pages 3-4) | Important complication-prevention and safety process measure |
| Care quality | In-hospital mortality for ischemic stroke | 5.8% → 4.2% | U.S. GWTG-Stroke registry; hospitalized ischemic stroke | 2003 → 2022 | Xian et al., Stroke (2024), https://doi.org/10.1161/STROKEAHA.124.048174 (xian2024twentyyearsof pages 4-5) | Risk-adjusted outcomes improved over time |
| Care quality | Discharge to home after ischemic stroke | 44.1% → 50.6% | U.S. GWTG-Stroke registry; hospitalized ischemic stroke | 2003 → 2022 | Xian et al., Stroke (2024), https://doi.org/10.1161/STROKEAHA.124.048174 (xian2024twentyyearsof pages 5-8) | Suggests improved short-term functional/disposition outcomes |
| Care quality | Discharge to skilled nursing facility after ischemic stroke | 20.9% → 13.6% | U.S. GWTG-Stroke registry; hospitalized ischemic stroke | 2003 → 2022 | Xian et al., Stroke (2024), https://doi.org/10.1161/STROKEAHA.124.048174 (xian2024twentyyearsof pages 5-8) | Decline consistent with better acute care and discharge outcomes |
Table: This table compiles recent quantitative ischemic stroke burden estimates and selected prevention/care-quality metrics from major 2024 sources. It is useful for quickly comparing global burden with real-world U.S. improvements in evidence-based stroke care delivery.
Ischemic stroke (also termed cerebral infarction) is caused primarily by thrombotic obstruction or embolic occlusion of cerebral vessels, leading to brain ischemia and tissue necrosis/infarction. (zhu2025globalandregional pages 1-5)
A widely used clinical/epidemiologic definition (as used in Global Burden of Disease [GBD] analyses aligned to WHO criteria) describes ischemic stroke as rapidly developing clinical signs of cerebral dysfunction due to occlusion of cerebral blood flow by thrombus/embolus, typically lasting >24 hours or leading to death; GBD also references the tissue-based concept of infarction-driven neurological dysfunction. (liu2025globalregionaland pages 1-2, liu2025epidemiologyandfuture pages 11-12)
This run did not retrieve OMIM/Orphanet/MeSH/ICD records directly; therefore, formal code mappings are not provided here and should be added from ontology resources (e.g., MeSH D-codes; ICD-10 I63.).*
Identifiers and abbreviations commonly used in the epidemiology literature include: IS (ischemic stroke), DALYs, ASIR (age-standardized incidence rate), ASMR (age-standardized mortality rate), ASDR (age-standardized DALY rate). (zhu2025globalandregional pages 16-19)
The evidence synthesized here is primarily from: - Aggregated, disease-level epidemiologic resources (GBD 2021–based analyses). (li2024globalregionaland pages 1-2, liu2025globalregionaland pages 1-2) - Aggregated clinical quality-improvement registry data (Get With The Guidelines–Stroke). (xian2024twentyyearsof pages 3-4) - Evidence-synthesizing clinical guideline documents (AHA/ASA 2024 primary prevention guideline). (bushnell20242024guidelinefor pages 2-3)
The proximal cause of ischemic stroke is cerebral blood flow interruption due to intravascular occlusion (thrombus/embolus), leading to ischemia and infarction/necrosis of downstream brain tissue. (zhu2025globalandregional pages 1-5, liu2025globalregionaland pages 1-2)
GBD 2021–based analyses consistently identify metabolic/vascular risks as dominant contributors to ischemic stroke burden. - High systolic blood pressure and high LDL-cholesterol were the leading modifiable contributors to DALYs over 1990–2021 in a GBD 2021 systematic analysis. (liu2025globalregionaland pages 1-2) - A GBD 2019–based analysis (Neurology, 2023) identified seven major attributable risk factors: smoking and high-sodium diet (behavioral), plus high systolic blood pressure, high LDL cholesterol, kidney dysfunction, high fasting plasma glucose, and high BMI (metabolic). (fan2023globalburdenrisk pages 1-2)
Environmental and behavioral factors are also highlighted in GBD-based syntheses, including air pollution and smoking. (liu2025epidemiologyandfuture pages 11-12, zhu2025globalandregional pages 16-19)
AHA/ASA’s 2024 primary prevention guideline endorses Mediterranean dietary patterns (with nuts and olive oil highlighted in the evidence synthesis) for stroke risk reduction. (bushnell20242024guidelinefor pages 2-3)
Not established from the retrieved evidence in this run. GBD and guideline sources emphasize risk-factor synergy (e.g., metabolic + behavioral risks) but do not provide specific validated gene–environment interaction effect estimates in the extracted passages. (fan2023globalburdenrisk pages 1-2, bushnell20242024guidelinefor pages 2-3)
The present run did not retrieve dedicated phenotype frequency studies or HPO-mapped clinical series; thus, phenotype frequencies and detailed HPO mapping are incomplete.
The defining clinical phenotype is an acute episode of neurological dysfunction due to focal infarction (classically focal deficits corresponding to vascular territory). (liu2025epidemiologyandfuture pages 11-12)
Large registry data show temporal improvements in discharge disposition after ischemic stroke (a proxy for early functional outcome): discharge to home increased from 44.1% (2003) to 50.6% (2022) and discharge to skilled nursing facilities decreased from 20.9% to 13.6% in GWTG-Stroke hospitals. (xian2024twentyyearsof pages 5-8)
These should be verified and frequency-annotated from primary clinical cohorts.
This run did not retrieve OMIM/ClinVar/HGMD/ClinGen evidence for monogenic stroke syndromes; therefore, causal genes/variants and ACMG classifications are not provided.
Ischemic stroke is described as a complex, multifactorial disorder with both environmental and heritable components; epidemiology sources emphasize that GBD-based analyses do not capture all genetic contributors. (fan2023globalburdenrisk pages 1-2, zhu2025globalandregional pages 16-19)
Environmental pollution is repeatedly identified as a major contributor alongside hypertension and LDL-cholesterol in GBD-based ischemic stroke risk-attribution summaries. (zhu2025globalandregional pages 1-5, zhu2025globalandregional pages 12-16)
Lifestyle and metabolic risks highlighted include smoking, high BMI, and high-sodium diet. (fan2023globalburdenrisk pages 1-2)
A canonical upstream-to-downstream chain supported by the retrieved evidence is: 1) Thrombotic/embolic occlusion of cerebral blood flow → 2) focal cerebral ischemia → 3) tissue infarction/necrosis → 4) acute neurological dysfunction and disability. (zhu2025globalandregional pages 1-5, liu2025globalregionaland pages 1-2)
Because this run emphasized epidemiology/guidelines, mechanistic molecular pathways (e.g., excitotoxicity, oxidative stress, BBB disruption) were not extracted from primary mechanistic papers here.
Suggested GO biological process terms (to be evidence-validated): - GO:0006954 inflammatory response - GO:0008219 cell death - GO:0006281 DNA repair (secondary injury context)
Suggested CL cell types (to be evidence-validated): - Microglial cell (CL:0000129) - Astrocyte (CL:0000127) - Brain microvascular endothelial cell (CL:2000064)
This run did not retrieve primary imaging guideline text or biomarker performance statistics; diagnostic details should be supplemented from acute stroke guideline documents and radiology literature.
The US Get With The Guidelines–Stroke (GWTG-Stroke) registry demonstrates large real-world improvements in evidence-based acute ischemic stroke workflows and secondary prevention processes from 2003–2022, including: - Anticoagulation for atrial fibrillation/flutter: 55.7% → 97.2%. - Smoking cessation counseling: 44.7% → 97.8%. - Dysphagia screening: 53.8% → 83.5%. - Arrive-by-3.5h/treat-by-4.5h thrombolysis measure: 15.2% → 92.9%. - Door-to-needle ≤60 min: 19.0% → 75.3%. These changes occurred across 7,837,849 stroke/TIA admissions from 2,865 hospitals and are presented as sustained improvements across performance measures. (xian2024twentyyearsof pages 3-4, xian2024twentyyearsof pages 1-2)
A figure depicting these temporal trends in key acute ischemic stroke care performance measures is provided in the source paper. (xian2024twentyyearsof media e6f60d86)
The AHA/ASA 2024 primary prevention guideline organizes prevention around the American Heart Association’s “Life’s Essential 8” domains: diet, physical activity, weight, sleep, blood sugar, blood pressure, lipids, and tobacco. (bushnell20242024guidelinefor pages 2-3)
Selected evidence-based prevention statements extracted from the guideline include: - Mediterranean diet is endorsed for stroke risk reduction (with nuts and olive oil emphasized in the evidence synthesis), while low-fat diets have shown little impact on stroke risk. (bushnell20242024guidelinefor pages 2-3) - Sedentary behavior: a new recommendation is to screen for sedentary behavior and counsel patients to avoid prolonged sedentary time. (bushnell20242024guidelinefor pages 2-3) - Blood pressure: randomized trial evidence summarized indicates single-drug BP control occurred in only ~30% of participants and most required 2–3 medications; accordingly, ≥2 antihypertensive medications are recommended when needed to achieve targets. (bushnell20242024guidelinefor pages 2-3)
Despite declining age-standardized mortality and DALY rates in many regions, absolute ischemic stroke case counts have increased substantially over 1990–2021 due to population growth and aging. (liu2025globalregionaland pages 1-2, zhu2025globalandregional pages 12-16)
Not established from retrieved evidence.
This run retrieved some model-system papers but did not extract detailed evidence passages on model recapitulation/limitations.
In-hospital mortality for ischemic stroke in GWTG-Stroke hospitals declined from 5.8% to 4.2% across 2003–2022, alongside shifting discharge patterns (more direct home discharge, fewer SNF discharges). (xian2024twentyyearsof pages 4-5, xian2024twentyyearsof pages 5-8)
Several requested knowledge-base fields (MONDO ID, ICD/MeSH codes, detailed phenotype frequencies with HPO mapping, causal genes/variants with ClinVar/gnomAD allele frequencies, and comprehensive diagnostics/treatment trial effect sizes) were not retrievable from the specific documents accessed in this run. The report should be extended by targeted retrieval from ontology databases (MONDO/MeSH/ICD), clinical guidelines for acute management, and primary genetics/biomarker studies.
References
(zhu2025globalandregional pages 1-5): Weimin Zhu, Xiaxia He, Daochao Huang, Yiqing Jiang, Weijun Hong, Shaofa Ke, En Wang, Feng Wang, Xianwei Wang, Renfei Shan, Suzhi Liu, Yinghe Xu, and Yongpo Jiang. Global and regional burden of ischemic stroke disease from 1990 to 2021: an age-period-cohort analysis. Translational stroke research, Dec 2025. URL: https://doi.org/10.1007/s12975-024-01319-9, doi:10.1007/s12975-024-01319-9. This article has 32 citations and is from a peer-reviewed journal.
(liu2025globalregionaland pages 1-2): Sibo Liu, Yanzhao Li, Xiaoyan Lan, Long Wang, Hang Li, Dean Gu, Mengxing Wang, and Jinjie Liu. Global, regional, and national trends in ischaemic stroke burden and risk factors among adults aged 20 + years (1990–2021): a systematic analysis of data from the global burden of disease study 2021 with projections into 2050. Frontiers in Public Health, Apr 2025. URL: https://doi.org/10.3389/fpubh.2025.1567275, doi:10.3389/fpubh.2025.1567275. This article has 23 citations.
(bushnell20242024guidelinefor pages 2-3): Cheryl Bushnell, Walter N. Kernan, Anjail Z. Sharrief, Seemant Chaturvedi, John W. Cole, William K. Cornwell, Christine Cosby-Gaither, Sarah Doyle, Larry B. Goldstein, Olive Lennon, Deborah A. Levine, Mary Love, Eliza Miller, Mai Nguyen-Huynh, Jennifer Rasmussen-Winkler, Kathryn M. Rexrode, Nicole Rosendale, Satyam Sarma, Daichi Shimbo, Alexis N. Simpkins, Erica S. Spatz, Lisa R. Sun, Vin Tangpricha, Dawn Turnage, Gabriela Velazquez, and Paul K. Whelton. 2024 guideline for the primary prevention of stroke: a guideline from the american heart association/american stroke association. Stroke, Dec 2024. URL: https://doi.org/10.1161/str.0000000000000475, doi:10.1161/str.0000000000000475. This article has 332 citations and is from a highest quality peer-reviewed journal.
(li2024globalregionaland pages 1-2): Xin-yu Li, Xiang-meng Kong, Cheng-hao Yang, Zhi-feng Cheng, Jia-jie Lv, Hong Guo, and Xiao-hong Liu. Global, regional, and national burden of ischemic stroke, 1990–2021: an analysis of data from the global burden of disease study 2021. eClinicalMedicine, 75:102758, Sep 2024. URL: https://doi.org/10.1016/j.eclinm.2024.102758, doi:10.1016/j.eclinm.2024.102758. This article has 309 citations and is from a peer-reviewed journal.
(xian2024twentyyearsof pages 3-4): Ying Xian, Shen Li, Tian Jiang, Chandler D. Beon, Remy Poudel, Kathie Thomas, Mathew J. Reeves, Eric E. Smith, Jeffrey L. Saver, Kevin N. Sheth, Steven R. Messé, Lee H. Schwamm, and Gregg C. Fonarow. Twenty years of sustained improvement in quality of care and outcomes for patients hospitalized with stroke or transient ischemic attack: data from the get with the guidelines-stroke program. Stroke, 55:2599-2610, Nov 2024. URL: https://doi.org/10.1161/strokeaha.124.048174, doi:10.1161/strokeaha.124.048174. This article has 23 citations and is from a highest quality peer-reviewed journal.
(xian2024twentyyearsof pages 1-2): Ying Xian, Shen Li, Tian Jiang, Chandler D. Beon, Remy Poudel, Kathie Thomas, Mathew J. Reeves, Eric E. Smith, Jeffrey L. Saver, Kevin N. Sheth, Steven R. Messé, Lee H. Schwamm, and Gregg C. Fonarow. Twenty years of sustained improvement in quality of care and outcomes for patients hospitalized with stroke or transient ischemic attack: data from the get with the guidelines-stroke program. Stroke, 55:2599-2610, Nov 2024. URL: https://doi.org/10.1161/strokeaha.124.048174, doi:10.1161/strokeaha.124.048174. This article has 23 citations and is from a highest quality peer-reviewed journal.
(xian2024twentyyearsof pages 4-5): Ying Xian, Shen Li, Tian Jiang, Chandler D. Beon, Remy Poudel, Kathie Thomas, Mathew J. Reeves, Eric E. Smith, Jeffrey L. Saver, Kevin N. Sheth, Steven R. Messé, Lee H. Schwamm, and Gregg C. Fonarow. Twenty years of sustained improvement in quality of care and outcomes for patients hospitalized with stroke or transient ischemic attack: data from the get with the guidelines-stroke program. Stroke, 55:2599-2610, Nov 2024. URL: https://doi.org/10.1161/strokeaha.124.048174, doi:10.1161/strokeaha.124.048174. This article has 23 citations and is from a highest quality peer-reviewed journal.
(xian2024twentyyearsof pages 5-8): Ying Xian, Shen Li, Tian Jiang, Chandler D. Beon, Remy Poudel, Kathie Thomas, Mathew J. Reeves, Eric E. Smith, Jeffrey L. Saver, Kevin N. Sheth, Steven R. Messé, Lee H. Schwamm, and Gregg C. Fonarow. Twenty years of sustained improvement in quality of care and outcomes for patients hospitalized with stroke or transient ischemic attack: data from the get with the guidelines-stroke program. Stroke, 55:2599-2610, Nov 2024. URL: https://doi.org/10.1161/strokeaha.124.048174, doi:10.1161/strokeaha.124.048174. This article has 23 citations and is from a highest quality peer-reviewed journal.
(liu2025epidemiologyandfuture pages 11-12): Jiayu Liu, Aoxi Xu, Zhifeng Zhao, Bin Ren, Zhao Gao, Dandong Fang, Bo Hei, Junzhao Sun, Xiangyang Bao, Lin Ma, Xiaoque Zheng, Yuxin Wang, Hecheng Ren, Guan Wang, Li Zhu, and Jianning Zhang. Epidemiology and future trend predictions of ischemic stroke based on the global burden of disease study 1990–2021. Communications Medicine, Jul 2025. URL: https://doi.org/10.1038/s43856-025-00939-y, doi:10.1038/s43856-025-00939-y. This article has 35 citations and is from a peer-reviewed journal.
(zhu2025globalandregional pages 16-19): Weimin Zhu, Xiaxia He, Daochao Huang, Yiqing Jiang, Weijun Hong, Shaofa Ke, En Wang, Feng Wang, Xianwei Wang, Renfei Shan, Suzhi Liu, Yinghe Xu, and Yongpo Jiang. Global and regional burden of ischemic stroke disease from 1990 to 2021: an age-period-cohort analysis. Translational stroke research, Dec 2025. URL: https://doi.org/10.1007/s12975-024-01319-9, doi:10.1007/s12975-024-01319-9. This article has 32 citations and is from a peer-reviewed journal.
(fan2023globalburdenrisk pages 1-2): Jiahui Fan, Xiaoguang Li, Xueying Yu, Zhenqiu Liu, Yanfeng Jiang, Yibin Fang, Ming Zong, Chen Suo, Qiuhong Man, and Lize Xiong. Global burden, risk factor analysis, and prediction study of ischemic stroke, 1990–2030. Neurology, Jul 2023. URL: https://doi.org/10.1212/wnl.0000000000207387, doi:10.1212/wnl.0000000000207387. This article has 433 citations and is from a highest quality peer-reviewed journal.
(zhu2025globalandregional pages 12-16): Weimin Zhu, Xiaxia He, Daochao Huang, Yiqing Jiang, Weijun Hong, Shaofa Ke, En Wang, Feng Wang, Xianwei Wang, Renfei Shan, Suzhi Liu, Yinghe Xu, and Yongpo Jiang. Global and regional burden of ischemic stroke disease from 1990 to 2021: an age-period-cohort analysis. Translational stroke research, Dec 2025. URL: https://doi.org/10.1007/s12975-024-01319-9, doi:10.1007/s12975-024-01319-9. This article has 32 citations and is from a peer-reviewed journal.
(xian2024twentyyearsof media e6f60d86): Ying Xian, Shen Li, Tian Jiang, Chandler D. Beon, Remy Poudel, Kathie Thomas, Mathew J. Reeves, Eric E. Smith, Jeffrey L. Saver, Kevin N. Sheth, Steven R. Messé, Lee H. Schwamm, and Gregg C. Fonarow. Twenty years of sustained improvement in quality of care and outcomes for patients hospitalized with stroke or transient ischemic attack: data from the get with the guidelines-stroke program. Stroke, 55:2599-2610, Nov 2024. URL: https://doi.org/10.1161/strokeaha.124.048174, doi:10.1161/strokeaha.124.048174. This article has 23 citations and is from a highest quality peer-reviewed journal.