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Stroke Risk Factors

Notes

Stroke Risk Factors

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Stroke Causes & Risk Factors

Definition of Stroke (& TIA)

Stroke & TIA

  • Both stroke and TIA (transient ischemic attack) involve focal neurological symptoms from a lack of cerebral perfusion (adequate blood flow).

Stroke

  • Stroke refers to an insult that produces permanent brain injury (even if the person fully recovers from the stroke deficits).

TIA (transient ischemic attack)

  • TIA is a transient phenomena that gets better on its own within 24 hours, without an MRI finding of stroke.
    Historically TIAs were treated less aggressively but now we lump them together in how we handle their diagnostic work-up and management, so the distinction is functionally unimportant.

Stroke Classifications

Ischemic vs Hemorrhagic Strokes

  • An ischemic stroke is a non-bleeding stroke and a hemorrhagic stroke is a bleeding stroke (a "brain bleed").
  • Roughly 85% of strokes are ischemic whereas 15% are hemorrhagic.

Petechial hemorrhages & Hemorrhagic conversion

  • Two potentially confusing entities are petechial hemorrhages and hemorrhagic conversion.
  • Roughly one-third (30 - 40%) of ischemic strokes will have some degree of bleeding (what we call petechial hemorrhagic changes). Think of these as bruising in the area of stroke injury. With any issue injury, tiny vessels can be damaged that will produce blood spots.
  • This is different than hemorrhagic conversion of an ischemic stroke. Hemorrhagic conversion is a stroke that starts out as an ischemic, non-bleeding stroke, but then develops secondary significant bleeding.

Embolic vs Thrombotic Infarcts

As far as the causes of ischemic stroke go, there are two key types:

  • Embolic (when a clot travels from the body and becomes lodged in the brain).
  • Thrombotic (when a clot forms within the brain vessel, itself).

Ischemic Stroke Classifications

We can further classify ischemic strokes as:

  • Cardioembolic [~ 25% of ischemic strokes], which is when a clot travels from the heart into the brain.
    • For instance, a cardiac embolus from atrial fibrillation.
  • Lacunar (small vessel disease), [~ 25% of ischemic strokes]. These small vessel clots can occur from lipohyalinosis (gradual clogging of the vessel from cardiovascular disease), atheromatous disease (atherosclerotic plaque), or an embolism that becomes lodged deep in the brain.
    • Think of a deep perforator infarct within the basal ganglia.
  • Watershed strokes, which refers to hypoperfusion (low flow) in the borderzone between arterial territories. This is an important, underreported phenomenon that occurs in the setting of low blood flow (from low blood pressure or blood loss). It has a specific pattern of affecting the proximal upper and lower extremities.
  • Cryptogenic [~ 33% of ischemic strokes], which means no identifiable cause can be determined.
  • Miscellaneous, which we can use to remember:

Hemorrhagic Strokes

We address hemorrhagic strokes elsewhere but briefly indicate that they can involve:

  • Intracerebral hematoma, meaning within the brain tissue, such as (most commonly) the basal ganglia or a cerebral lobe, or other areas including (notably) the thalamus, pons, or cerebellum.
  • Extracerebral/intracranial hemorrhages, which are bleeds outside of the brain tissue but still within the skull (within the cranial vault). These are, primarily:

Stroke Risk Factors

  • Please refer to the Stroke Prevention in Patients With Stroke and TIA and the Guidelines for the Primary Prevention of Stroke both published in Stroke from 2014 for complete recommendations.
    • What follows are some helpful considerations for clinicians that were pulled together from the both 2014 Guidelines and some additional references; this information is not exhaustive and is simply designed for efficient review.

Major Modifiable Risk Factors for Stroke

Hypertension (Blood Pressure > 140/90)

  • Goal BP is < 140/90 but specific target for each patient must be individualized.
  • No particular anti-hypertensive agent is preferred (2014 Secondary Stroke Prevention Guidelines).

Dyslipidemia (hypercholesterolemia) (LDL-C > 100 mg/dL)

  • Statin therapy, specifically, is recommended in the treatment of hypercholesterolemia.
  • The 2014 Secondary Stroke Prevention Guidelines comment on the lack of data to support a specific target LDL level but do acknowledge that post-hoc analysis of the SPARCL trial demonstrated that when an LDL-C of <70 mg/dL is achieved, there is a 28% reduction in risk of stroke without a significant rise in hemorrhagic stroke.

Diabetes mellitus

  • Following the standard ADA guidelines in the management of DM is recommended.

Tobacco abuse

OSA

  • OSA treatment is recommended because of its clear overall benefits, but treatment of OSA has not yet been proven to reduce secondary vascular events.

Carotid artery stenosis

  • For symptomatic severe carotid artery stenosis (70 – 99% stenosis), carotid endartectomy (CEA) is recommended (if the peri-operative morbidity and mortality risk is estimated to be <6%).
  • For symptomatic moderate (50%–69%) carotid stenosis, the benefits are less robust and thus careful patient selection plays an important factor in the decision for CEA.
  • The 2014 guidelines comment that carotid stenting may be reasonable in patients younger than 70 years old and in certain conditions (eg, radiation-induced stenosis or restenosis after CEA).

Atrial fibrillation (See below)

Obesity

  • Weight loss is recommended but it has been difficult to tease out the specific benefits to stroke because of the improvement that occurs to other modifiable risk factors when patients lose weight.

Physical inactivity

  • Exercise 40 min a day, 3-4 d/wk is recommended.

Nutrition

  • A Mediterranean diet supplemented with nuts and diets rich in fruits, vegetables, saturated fats and total fats are recommended to reduce stroke risk (in part due to their effects on BP reduction).
  • Low-sodium diets, specifically, are recommended to reduce BP (especially in African American patients).

Cardioembolic Etiologies

Cardioembolic strokes account for 20-30% of all ischemic strokes. Atrial fibrillation is the most significant cardioembolic stroke risk factor.

Arrhythmias

  • Atrial Fibrillation
    • Blood clots typically form in the left atrium or left atrial appendage.
    • Atrial flutter carries the same risk for stroke as atrial fibrillation.
    • Anticoagulation is the mainstay of treatment for secondary stroke prevention.
      In patients in whom anticoagulation is contraindicated (eg, lobar hemorrhages), left atrial appendage closure is an alternative treatment.
    • For primary stroke prevention, the CHA2DS2-VASc Risk Criteria are used to determine whether oral anticoagulants pose an overall benefit or harm in non-valvular A Fib.
      In short, any of the below risk factors makes oral anticoagulation a reasonable option for stroke prevention and if there is any major risk factor or 2 or more minor risk factors, oral anticoagulation becomes a must (barring contraindication).
      Major RFs: Age >75 yr, History of Stroke/TIA/Thromboembolism
      Minor RFs: CHF, HTN, DM, Vascular disease, Age 65-74, Female sex

Cardiac Thrombus Formation in the Setting of Stasis of Blood Flow

  • Left ventricular thrombus can form secondary to MI or CHF (especially from acute anterior wall dysfunction or apical akinesis).
    • Anticoagulation may be considered for patients with STEMI and anterior apical akinesis or dyskinesis.
  • Cardiomyopathy (ventricular assist devices can lead to thrombus formation).

Cardiac Tumors

  • Atrial myxomas (account for ~ 50% of cardiac tumors)
    • Thrombus can form on the tumor, itself, which can then embolize.
    • Alternatively, the myxomatous material, itself, can embolize.
    • Surgical removal is recommended.
  • Papillary fibroelastomas (most commonly on the aortic valve) can cause stroke.
    • Surgical intervention is recommended for symptomatic fibroelastomas and for fibroelastomas that are >1 cm or appear mobile (even if asymptomatic).

Paradoxical Embolism

  • Patent Foramen Ovale (PFO)
    • PFO is a residual communication between the right and left atria from the time of fetal circulation (when this is a requisite communication).
    • 25% to 30% of the population has a PFO.
    • PFO can result in thrombus formation at the communication site or cause stroke via paradoxical embolism of a DVT.
    • There is likely a benefit to percutaneous closure in patients with larger, higher volume right-to-left shunts, especially if they are young and have no other stroke risk factors or history of stroke.
      The Risk of Paradoxical Embolism (RoPE) score is a way to assess the relevance of a patient's PFO.
      Younger patients with no other cause of stroke of history of stroke have a high RoPE score and thus those patients will presumably benefit the most from PFO treatment (ie, closure).

Valvular Disease

  • Prosthetic artificial valves have a higher risk of causing clot formation and stroke than do bioprosthetic valves.
    • Anticoagulation is recommended for patients with prosthetic valves and in patients with bioprosthetic valves IF they have any other significant stroke risk factors.
    • However, after the first 3 months post valve replacement, patients with bioprosthetic valves and no other significant stroke risk factors, can be treated with aspirin, alone.
  • Endocarditis can produce septic emboli.
    • Due to the risk of mycotic aneurysms and intracranial hemorrhage, anticoagulation is not recommended in the setting of endocarditis.
  • Rheumatic disease and annular calcifications can lead to clot formation, especially if there is resultant mitral stenosis.
  • Mitral stenosis
    • Anticoagulation is recommended in the setting of mitral stenosis and a prior embolic event and a known left atrial thrombus, and it may be considered when there is mitral stenosis and left atrial enlargement.

Aortic Arch Disease

  • Aortic arch atheroma is an important cause of stroke.
  • Aortic dissection (Type A, (ascending aorta)) can result in stroke.
    • In addition to cerebral ischemia, spinal cord infarcts can occur from aortic dissection.
    • Horner's syndrome can be clue to aortic dissection when the dissection extends into a carotid artery.

Thrombophilias

Most hypercoagulable states are known to cause venous thromboembolism, not arterial occlusion, thus routine testing for the inherited thrombophilias is not recommended.

Inherited thrombophilias

Known to cause venous clot formation

  • Factor V Leiden
  • Prothrombin gene mutation
  • Protein C deficiency
  • Protein S deficiency
  • Antithrombin III deficiency
  • Activated protein C resistance
  • Prothrombin mutation
  • Hyperhomocysteinemia (especially from methylenetetrahydrofolate reductase (MTHFR) mutations.
    Testing for these conditions is generally only recommended when there is a personal or family history of systemic thrombosis or in cryptogenic stroke in young patients.

Autoimmune Disorders

  • Antiphospholipid antibody syndrome
    • Associated with both arterial and venous thrombosis.
    • Antiphospholipid antibody syndrome when there is clinical suspicion for the syndrome.

Common Hypercoagulable States of Health

  • Pregnancy
  • Malignancy

Common Iatrogenic Causes of Hypercoagulability

  • Oral contraceptives
  • Hormone replacement therapy

Stroke Risk After TIA: ABCD2 Score

  • Age - 60 yo or greater
    • 1 point
  • SBP - 140 mmHg or greater or DBP - 90 mmHg or greater
    • 1 point
  • Clinical Features of the TIA
    • 2 points if there is unilateral weakness
    • 1 point if there is speech impairment without unilateral weakness
  • Duration
    • 2 points if the duration is 60 minutes or greater
    • 1 point if the duration is 10-59 minutes
  • Diabetes mellitus
    • 1 point
  • Score of 0-3 confers a 1% risk of stroke within 48 hours
  • Score of 4-5 confers a 4.1% risk of stroke within 48 hours
  • Score of 6-7 confers a 8.1% risk of stroke within 48 hours

References

  • Grysiewicz RA, Thomas K, Pandey DK. Epidemiology of ischemic and hemorrhagic stroke: incidence, prevalence, mortality, and risk factors. Neurol Clin 2008; 26:871.
  • Kelly, Adam. Cerebrovascular Disorders. American Academy of Neurology Institute. 2016.
  • Klaas, James, P. Neurologic Complications of Cardiac and Aortic Disease. CONTINUUM: Lifelong Learning in Neurology: June 2017 - Volume 23 - Issue 3, Neurology of Systemic Disease - p 654–668
  • Kernan WN, Ovbiagele B, Black HR, et al. Guidelines for the prevention of stroke in patients with stroke and transient ischemic attack: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2014; 45:2160.
  • Meschia, James F., Bushnell, Cheryl, Boden-Albala, Bernadette, et. al Guidelines for the Primary Prevention of Stroke: A Statement for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke 2014; October 28, 2014
  • O'Donnell MJ, Chin SL, Rangarajan S, et al. Global and regional effects of potentially modifiable risk factors associated with acute stroke in 32 countries (INTERSTROKE): a case-control study. Lancet 2016; 388:761.
  • Powers, William J., Rabinstein, Alejandro A., Ackerson, Teri, et. al. 2018 Guidelines for the Early Management of Patients With Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association Stroke 2018; January 24, 2018