⚙

Pathophysiology

4

Cerebral arterial occlusion

In situ thrombosis, artery-to-artery embolism, cardioembolism, or proximal large-vessel occlusion interrupts cerebral blood flow and initiates the ischemic cascade.

endothelial cell CL:0000115

blood coagulation GO:0007596 ↑ INCREASED platelet aggregation GO:0070527 ↑ INCREASED

Downstream

Ischemic penumbra and energy failure Occlusion creates a severely hypoperfused core and a potentially salvageable penumbra with residual perfusion.

Show evidence (1 reference)

PMID:20670828 SUPPORT Human Clinical

"This can develop either as a consequence of thrombosis in situ or following embolic occlusion of a cerebral blood vessel"

This review supports thrombosis and embolic vascular occlusion as proximal ischemic-stroke mechanisms.

Ischemic penumbra and energy failure

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.

neuron CL:0000540 astrocyte CL:0000127 endothelial cell CL:0000115

response to hypoxia GO:0001666 ↑ INCREASED cell death GO:0008219 ↑ INCREASED

Downstream

Excitotoxic and oxidative neuronal injury Energy failure disrupts ionic gradients and glutamate handling, triggering calcium overload, oxidative injury, and cell death.

Neurovascular inflammation and barrier disruption Ischemic injury activates vascular, glial, and immune responses in the neurovascular unit.

Show evidence (2 references)

PMID:21628695 SUPPORT Human Clinical

"In ischemic strokes, severe blood flow deficits in the core rapidly decrease ATP levels and energy stores."

This supports energy failure as an early consequence of ischemic core hypoperfusion.

PMID:20670828 SUPPORT Human Clinical

"The ischemic penumbra then denotes an “at risk” region that is functionally impaired, but potentially salvageable."

This supports the penumbra as an at-risk but potentially salvageable tissue compartment.

Excitotoxic and oxidative neuronal injury

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.

neuron CL:0000540

response to oxidative stress GO:0006979 ↑ INCREASED apoptotic process GO:0006915 ↑ INCREASED

Show evidence (2 references)

PMID:21628695 SUPPORT Human Clinical

"accumulated data over the past two decades have implicated excitotoxicity, oxidative stress and in some circumstances, apoptotic-like pathways"

This supports excitotoxic, oxidative, and apoptotic-like injury processes in acute stroke cell death.

PMID:28417216 SUPPORT Human Clinical

"Brain injury following stroke results from a complex series of pathophysiological events including excitotoxicity, oxidative and nitrative stress, inflammation, and apoptosis."

This review independently supports the multi-mechanism cellular injury cascade after ischemic stroke.

Neurovascular inflammation and barrier disruption

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.

endothelial cell CL:0000115 astrocyte CL:0000127 microglial cell CL:0000129

inflammatory response GO:0006954 ↑ INCREASED cell-cell signaling GO:0007267 ⚠ ABNORMAL

Show evidence (2 references)

PMID:21738161 SUPPORT Human Clinical

"Inflammatory signaling is involved in all stages of the ischemic cascade, from the early damaging events triggered by arterial occlusion"

This supports inflammation as a contributor from early post-occlusion injury through later repair.

PMID:21628695 SUPPORT Human Clinical

"The BBB homeostasis is remarkably dependent on endothelial-astrocyte-matrix interactions"

This supports endothelial-astrocyte-matrix interactions as central to blood-brain barrier integrity after stroke.

⬡

Pathograph

Use the checkboxes to hide or show graph categories. Hover nodes for evidence and cross-linked metadata.

●

Phenotypes

5

Cardiovascular 1

Symptomatic central nervous system infarction Ischemic stroke HP:0002140

Show evidence (1 reference)

PMID:23652265 SUPPORT Human Clinical

"Ischemic stroke specifically refers to central nervous system infarction accompanied by overt symptoms"

This consensus definition directly supports the diagnostic phenotype.

Digestive 1

Dysphagia HP:0002015

Show evidence (1 reference)

PMID:39342159 SUPPORT Human Clinical

"Of 2054 patients with ischemic stroke, 17.2% showed dysphagia at hospital admission."

This acute ischemic stroke cohort supports dysphagia as a clinically important swallowing phenotype.

Nervous System 3

Hemiparesis HP:0001269

Show evidence (1 reference)

PMID:35204601 SUPPORT Human Clinical

"secondary signs, namely hemiparesis with limb falls (P), aphasia (A), drowsy or worse consciousness (C), and eyeball limitation"

This acute ischemic stroke cohort used hemiparesis with limb falls as a stroke severity sign.

Aphasia HP:0002381

Show evidence (1 reference)

PMID:32173230 SUPPORT Human Clinical

"Aphasia is one of the most severe symptoms in stroke patients, affecting one-third of acute stroke patients."

This national inpatient analysis supports aphasia as a major acute ischemic stroke symptom.

Dysarthria HP:0001260

Show evidence (1 reference)

PMID:33580596 SUPPORT Human Clinical

"46% (70/151) of participants had dysarthria, of which half recovered completely from their dysarthria within 1 week"

This prospective acute ischemic stroke study supports dysarthria as a common acute speech phenotype.

💊

Medical Actions

5

Intravenous t-PA thrombolysis

Action: Pharmacotherapy NCIT:C15986

Agent: alteplase NCIT:C39607

Intravenous tissue plasminogen activator can restore perfusion in eligible early-presenting patients, improving 3-month functional outcome while increasing symptomatic intracerebral hemorrhage risk.

Mechanism Target:

INHIBITS Cerebral arterial occlusion — Thrombolysis aims to dissolve the occluding thrombus and restore cerebral perfusion.

Show evidence (2 references)

PMID:7477192 SUPPORT Human Clinical

"treatment with intravenous t-PA within three hours of the onset of ischemic stroke improved clinical outcome at three months."

This randomized trial established early IV t-PA benefit in acute ischemic stroke.

PMID:36123777 SUPPORT Other

"Consistent with this weak recommendation, optimal patient management will likely often include co-treatment with intravenous alteplase, depending on local circumstances and patient presentation."

The clinical practice guideline supports co-treatment with intravenous alteplase (t-PA) alongside endovascular thrombectomy in acute large-vessel-occlusion ischemic stroke.

Endovascular thrombectomy

Action: surgical procedure Ontology label: Surgical Procedure NCIT:C15329

Endovascular clot retrieval improves disability outcomes in selected patients with acute ischemic stroke caused by proximal anterior-circulation large-vessel occlusion.

Mechanism Target:

INHIBITS Cerebral arterial occlusion — Mechanical clot retrieval removes the proximal occlusion and restores blood flow in large-vessel ischemic stroke.

Show evidence (1 reference)

PMID:26898852 SUPPORT Human Clinical

"Endovascular thrombectomy led to significantly reduced disability at 90 days compared with control"

This pooled randomized-trial analysis supports thrombectomy for selected large-vessel ischemic stroke.

Antiplatelet secondary prevention

Action: Pharmacotherapy NCIT:C15986

Agent: Antiplatelet Agent NCIT:C1327

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.

Mechanism Target:

MODULATES Cerebral arterial occlusion — Platelet inhibition reduces recurrent thrombotic arterial occlusion risk after qualifying ischemic stroke presentations.

Show evidence (1 reference)

PMID:34024115 SUPPORT Human Clinical

"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."

This systematic review supports antiplatelet therapy as secondary prevention after selected ischemic stroke or high-risk TIA presentations.

Anticoagulation for atrial fibrillation-associated stroke prevention

Action: Pharmacotherapy NCIT:C15986

Agent: Anticoagulant Agent NCIT:C263

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.

Mechanism Target:

MODULATES Cerebral arterial occlusion — Anticoagulation reduces cardioembolic clot formation that can occlude cerebral arteries in atrial fibrillation-associated ischemic stroke.

Show evidence (1 reference)

PMID:31984228 SUPPORT Human Clinical

"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."

This guideline supports oral anticoagulation for secondary prevention in atrial fibrillation-associated ischemic stroke or TIA.

Primary prevention through vascular risk-factor control

Action: supportive care Ontology label: Supportive Care NCIT:C15747

Stroke prevention focuses on cardiovascular and brain-health domains including diet, activity, weight, sleep, glycemic control, blood pressure, lipids, and tobacco avoidance.

Mechanism Target:

MODULATES Cerebral arterial occlusion — Risk-factor control reduces the vascular conditions that promote thrombotic and embolic stroke.

Show evidence (1 reference)

PMID:39429201 SUPPORT Human Clinical

"These recommendations align with the American Heart Association's Life's Essential 8 for optimizing cardiovascular and brain health"

This guideline supports multi-domain vascular risk-factor control for primary stroke prevention.

🌍

Environmental Factors

1

Vascular and metabolic risk-factor burden

Smoking, high-sodium diet, hypertension, high LDL cholesterol, kidney dysfunction, hyperglycemia, and high BMI are major modifiable contributors to ischemic stroke burden.

Show evidence (1 reference)

PMID:37197995 SUPPORT Computational

"2 behavioral factors, smoking and diet in high sodium, and 5 metabolic factors, including high systolic blood pressure"

This GBD risk-factor analysis supports behavioral and metabolic contributors to ischemic stroke burden.

📊

Prevalence

1

Global, all ages

GBD 2021 estimated about 69.9 million prevalent ischemic stroke cases globally, with an age-standardized prevalence rate of 819.5 per 100,000.

Show evidence (1 reference)

PMID:39157811 SUPPORT Computational

"In 2021, the global burden of ischemic stroke remained substantial, with a total of 69,944,884.8 cases"

GBD modeled estimates support the high global prevalence of ischemic stroke.

📊

Related Datasets

6

Transfer RNAs, not microRNAs, are linked to ischemic stroke and major bleeding in patients with end-stage kidney disease geo:GSE272125

Background: Patients with end-stage kidney disease (ESKD) are at very high risk for thromboembolism and bleeding. This study aimed to identify small non-coding RNAs (sncRNAs), specifically microRNAs and transfer-RNA (tRNA)-derived fragments (tRFs), as potential novel biomarkers for predicting thromboembolism and bleeding in this high-risk population. Methods: In this sncRNA discovery research, we leveraged the VIVALDI cohort, consisting of 625 ESKD patients on hemodialysis, to conduct two nested case-control studies, each comprising 18 participants. The primary outcomes were ischemic stroke in the first study and major bleeding in the second.

human BULK RNA SEQ n=34

PMID:39260398

Identified by GEO DataSets index search for Ischemic Stroke (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values.

Ischemic stroke accelerates atherosclerosis progression via FTO-mediated epigenetic modification [RNA-Seq] geo:GSE308369

Residual risk of stroke recurrence persists despite the administration of the prevention measures. The recurrent risk is particularly high in patients with atherosclerosis. However, the underlying mechanisms leading to atherosclerosis progression and recurrent stroke have not been fully understood. We found that stroke accelerated atherosclerosis progression.

human BULK RNA SEQ n=8

Identified by GEO DataSets index search for Ischemic Stroke (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values.

Ischemic stroke accelerates atherosclerosis progression via FTO-mediated epigenetic modification geo:GSE307081

Residual risk of stroke recurrence persists despite the administration of the prevention measures. The recurrent risk is particularly high in patients with atherosclerosis. However, the underlying mechanisms leading to atherosclerosis progression and recurrent stroke have not been fully understood. We found that stroke accelerated atherosclerosis progression.FTO overexpression suppressed atheroprogression after stroke via inhibiting autophagy-dependent ferroptosis.

human BULK RNA SEQ n=7

Identified by GEO DataSets index search for Ischemic Stroke (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values.

A genome-wide meta analysis on stroke and ischemic stroke within four populations ega:EGAS00000000060

In this analysis a genome-wide meta-analysis was performed on all stroke and ischemic stroke.

human

European Genome-phenome Archive study, matched because the disease is named in the study's own title ("Ischemic Stroke"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01.

Ischemic stroke in a Swedish case-control study. ega:EGAS00001000936

Background. Genetic risk scores (GRS), summing up the total effect of several single nucleotide polymorphisms (SNPs) in genes associated with either coronary risk or cardiovascular risk factors, have been tested for association with ischemic stroke with conflicting results. Recently an association was found between a GRS, based on 29 SNPs discovered by genome-wide association studies (GWAS) and hypertension. The aim of our study was to investigate the possible association of the same GRS with ischemic stroke on top of other “traditional risk factors”, also testing its potential improvement in indices of discrimination and reclassification, in a Swedish case-control study.

human

European Genome-phenome Archive study, matched because the disease is named in the study's own title ("Ischemic Stroke"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01.

Ischemic Stroke Genetics Study (ISGS) dbgap:phs000102

The third leading cause of death in the United States, stroke is an acute neurological event leading to death of neural tissues. Although the majority of strokes are ischemic strokes, meaning there is oxygen deprivation to the brain, almost 20% of strokes are hemorrhagic, resulting from bleeding into the brain. Stroke is a complex disorder and likely multigenic in nature, resulting from a combination of genetic and environmental factors.

Located via OmicsDI, which aggregates across omics repositories; this record comes from dbgap. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title ("Ischemic Stroke"). Retrieved 2026-08-02.

{ }

Source YAML

click to show

name: Ischemic Stroke
creation_date: "2026-05-06T03:10:37Z"
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.
  - reference: PMID:36123777
    reference_title: "Endovascular thrombectomy and intravenous alteplase in patients with acute ischemic stroke due to large vessel occlusion: A clinical practice guideline."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Consistent with this weak recommendation, optimal patient management will likely often include co-treatment with intravenous alteplase, depending on local circumstances and patient presentation."
    explanation: The clinical practice guideline supports co-treatment with intravenous alteplase (t-PA) alongside endovascular thrombectomy in acute large-vessel-occlusion 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.
  therapeutic_modality: SURGERY
  treatment_term:
    preferred_term: surgical procedure
    term:
      id: NCIT:C15329
      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: NCIT:C15747
      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:
- accession: geo:GSE272125
  title: Transfer RNAs, not microRNAs, are linked to ischemic stroke and major bleeding in patients with end-stage kidney disease
  description: 'Background: Patients with end-stage kidney disease (ESKD) are at very high risk for thromboembolism and bleeding. This study aimed to identify small non-coding RNAs (sncRNAs), specifically microRNAs and transfer-RNA (tRNA)-derived fragments (tRFs), as potential novel biomarkers for predicting thromboembolism and bleeding in this high-risk population. Methods: In this sncRNA discovery research, we leveraged the VIVALDI cohort, consisting of 625 ESKD patients on hemodialysis, to conduct two nested case-control studies, each comprising 18 participants. The primary outcomes were ischemic stroke in the first study and major bleeding in the second.'
  organism:
    preferred_term: human
    term:
      id: NCBITaxon:9606
      label: Homo sapiens
  data_type: BULK_RNA_SEQ
  sample_count: 34
  publication: PMID:39260398
  notes: Identified by GEO DataSets index search for Ischemic Stroke (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values.
- accession: geo:GSE308369
  title: Ischemic stroke accelerates atherosclerosis progression via FTO-mediated epigenetic modification [RNA-Seq]
  description: Residual risk of stroke recurrence persists despite the administration of the prevention measures. The recurrent risk is particularly high in patients with atherosclerosis. However, the underlying mechanisms leading to atherosclerosis progression and recurrent stroke have not been fully understood. We found that stroke accelerated atherosclerosis progression.
  organism:
    preferred_term: human
    term:
      id: NCBITaxon:9606
      label: Homo sapiens
  data_type: BULK_RNA_SEQ
  sample_count: 8
  notes: Identified by GEO DataSets index search for Ischemic Stroke (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values.
- accession: geo:GSE307081
  title: Ischemic stroke accelerates atherosclerosis progression via FTO-mediated epigenetic modification
  description: Residual risk of stroke recurrence persists despite the administration of the prevention measures. The recurrent risk is particularly high in patients with atherosclerosis. However, the underlying mechanisms leading to atherosclerosis progression and recurrent stroke have not been fully understood. We found that stroke accelerated atherosclerosis progression.FTO overexpression suppressed atheroprogression after stroke via inhibiting autophagy-dependent ferroptosis.
  organism:
    preferred_term: human
    term:
      id: NCBITaxon:9606
      label: Homo sapiens
  data_type: BULK_RNA_SEQ
  sample_count: 7
  notes: Identified by GEO DataSets index search for Ischemic Stroke (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-07-31. Title, sample count, and organism are GEO's own values.
- accession: ega:EGAS00000000060
  title: A genome-wide meta analysis on stroke and ischemic stroke within four populations
  description: In this analysis a genome-wide meta-analysis was performed on all stroke and ischemic stroke.
  organism:
    preferred_term: human
    term:
      id: NCBITaxon:9606
      label: Homo sapiens
  notes: 'European Genome-phenome Archive study, matched because the disease is named in the study''s own title ("Ischemic Stroke"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01.'
- accession: ega:EGAS00001000936
  title: Ischemic stroke in a Swedish case-control study.
  description: Background. Genetic risk scores (GRS), summing up the total effect of several single nucleotide polymorphisms (SNPs) in genes associated with either coronary risk or cardiovascular risk factors, have been tested for association with ischemic stroke with conflicting results. Recently an association was found between a GRS, based on 29 SNPs discovered by genome-wide association studies (GWAS) and hypertension. The aim of our study was to investigate the possible association of the same GRS with ischemic stroke on top of other “traditional risk factors”, also testing its potential improvement in indices of discrimination and reclassification, in a Swedish case-control study.
  organism:
    preferred_term: human
    term:
      id: NCBITaxon:9606
      label: Homo sapiens
  notes: 'European Genome-phenome Archive study, matched because the disease is named in the study''s own title ("Ischemic Stroke"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01.'
- accession: dbgap:phs000102
  title: Ischemic Stroke Genetics Study (ISGS)
  description:  The third leading cause of death in the United States, stroke is an acute neurological event leading to death of neural tissues. Although the majority of strokes are ischemic strokes, meaning there is oxygen deprivation to the brain, almost 20% of strokes are hemorrhagic, resulting from bleeding into the brain. Stroke is a complex disorder and likely multigenic in nature, resulting from a combination of genetic and environmental factors.
  notes: Located via OmicsDI, which aggregates across omics repositories; this record comes from dbgap. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title ("Ischemic Stroke"). Retrieved 2026-08-02.

📚

References & Deep Research

Deep Research

1

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Ischemic Stroke (Complex Disease) — Disease Characteristics Research Report

Edison Scientific Literature 25 citations 2026-05-05T23:25:09.211664

Ischemic Stroke (Complex Disease) — Disease Characteristics Research Report

Executive summary

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.

1. Disease Information

1.1 Definition / overview (current understanding)

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)

1.2 Key identifiers (available from retrieved sources)

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)

1.3 Common synonyms / alternative names

Ischemic stroke (IS) (liu2025globalregionaland pages 1-2)
Cerebral infarction (zhu2025globalandregional pages 1-5)

1.4 Source of information

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)

2. Etiology

2.1 Disease causal factors (mechanistic framing)

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)

2.2 Risk factors (recent quantitative summaries)

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)

2.3 Protective factors

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)

2.4 Gene–environment interactions

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)

3. Phenotypes

The present run did not retrieve dedicated phenotype frequency studies or HPO-mapped clinical series; thus, phenotype frequencies and detailed HPO mapping are incomplete.

3.1 Core phenotype concept (high-level)

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)

3.2 Quality-of-life impact (system-level proxy)

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)

3.3 Suggested HPO terms (placeholders; not evidence-mapped in this run)

Hemiparesis (HP:0001269)
Aphasia (HP:0002381)
Dysarthria (HP:0001260)
Dysphagia (HP:0002015)
Visual field defect (HP:0001123)

These should be verified and frequency-annotated from primary clinical cohorts.

4. Genetic / Molecular Information

This run did not retrieve OMIM/ClinVar/HGMD/ClinGen evidence for monogenic stroke syndromes; therefore, causal genes/variants and ACMG classifications are not provided.

4.1 Current understanding (complex genetics)

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)

5. Environmental Information

5.1 Environmental factors

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)

5.2 Lifestyle factors

Lifestyle and metabolic risks highlighted include smoking, high BMI, and high-sodium diet. (fan2023globalburdenrisk pages 1-2)

6. Mechanism / Pathophysiology

6.1 Causal chain (macro-to-micro)

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)

6.2 Biological processes and cell types (ontology suggestions; limited direct evidence in this run)

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)

7. Diagnostics

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.

8. Treatment

8.1 Real-world implementation and systems of care

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)

8.2 MAXO terms (suggested; not formally mapped in this run)

Thrombolysis (MAXO:0001294)
Mechanical thrombectomy / endovascular thrombectomy (MAXO term to be confirmed)
Anticoagulant therapy (MAXO:0000436)
Antiplatelet therapy (MAXO:0000435)
Dysphagia screening/intervention (MAXO term to be confirmed)

9. Prevention

9.1 Primary prevention (AHA/ASA 2024 guideline highlights)

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)

9.2 Population-health rationale from burden data

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)

10. Other Species / Natural Disease

Not established from retrieved evidence.

11. Model organisms

This run retrieved some model-system papers but did not extract detailed evidence passages on model recapitulation/limitations.

12. Outcomes / Prognosis

12.1 Registry-based short-term outcome trends (US)

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)

13–15. Remaining template elements

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.

Direct quotes from abstracts (for key statements)

AHA/ASA 2024 prevention guideline aim: “Ischemic and hemorrhagic strokes lead to significant disability but, most important, are preventable.” (bushnell20242024guidelinefor pages 2-3)
GWTG-Stroke scale and performance improvement: the registry included “7,837,849 stroke cases… [and] sustained improvement in all performance metrics” with examples including “anticoagulation for atrial fibrillation (55.7% in 2003 to 97.2% in 2022)” and “door-to-needle time within 60 minutes (19.0%–75.3%).” (xian2024twentyyearsof pages 3-4)

Key URLs and publication dates (from retrieved sources)

Li et al. “Global, regional, and national burden of ischemic stroke, 1990–2021…” eClinicalMedicine; published Sep 2024. https://doi.org/10.1016/j.eclinm.2024.102758 (li2024globalregionaland pages 1-2)
Bushnell et al. “2024 Guideline for the Primary Prevention of Stroke…” Stroke; published Dec 2024. https://doi.org/10.1161/str.0000000000000475 (bushnell20242024guidelinefor pages 2-3)
Xian et al. “Twenty Years of Sustained Improvement…” Stroke; published Nov 2024. https://doi.org/10.1161/strokeaha.124.048174 (xian2024twentyyearsof pages 3-4)

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.

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Pathophysiology

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Phenotypes

Medical Actions

Environmental Factors

Prevalence

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References & Deep Research

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Ischemic Stroke (Complex Disease) — Disease Characteristics Research Report

Executive summary

1. Disease Information

1.1 Definition / overview (current understanding)

1.2 Key identifiers (available from retrieved sources)

1.3 Common synonyms / alternative names

1.4 Source of information

2. Etiology

2.1 Disease causal factors (mechanistic framing)

2.2 Risk factors (recent quantitative summaries)

2.3 Protective factors

2.4 Gene–environment interactions

3. Phenotypes

3.1 Core phenotype concept (high-level)

3.2 Quality-of-life impact (system-level proxy)

3.3 Suggested HPO terms (placeholders; not evidence-mapped in this run)

4. Genetic / Molecular Information

4.1 Current understanding (complex genetics)

5. Environmental Information

5.1 Environmental factors

5.2 Lifestyle factors

6. Mechanism / Pathophysiology

6.1 Causal chain (macro-to-micro)

6.2 Biological processes and cell types (ontology suggestions; limited direct evidence in this run)

7. Diagnostics

8. Treatment

8.1 Real-world implementation and systems of care

8.2 MAXO terms (suggested; not formally mapped in this run)

9. Prevention

9.1 Primary prevention (AHA/ASA 2024 guideline highlights)

9.2 Population-health rationale from burden data

10. Other Species / Natural Disease

11. Model organisms

12. Outcomes / Prognosis

12.1 Registry-based short-term outcome trends (US)

13–15. Remaining template elements

Direct quotes from abstracts (for key statements)

Key URLs and publication dates (from retrieved sources)