Risk Factors for Acute Ischemic Stroke
Acute ischemic stroke risk factors are systematically classified into nonmodifiable factors (age, sex, race/ethnicity, genetics) and modifiable factors, with hypertension being the single most important modifiable risk factor, followed by atrial fibrillation, diabetes, dyslipidemia, smoking, physical inactivity, and obesity. 1, 2
Nonmodifiable Risk Factors
Age is the most powerful nonmodifiable risk factor, with stroke risk doubling for each decade after age 55 years 2. This continuous relationship means that an 85-year-old has approximately 8 times the stroke risk of a 55-year-old, independent of other factors 1.
Sex influences stroke risk differently across the lifespan, with men having higher rates at younger ages but women experiencing more strokes overall due to longer life expectancy 1, 2.
Race and ethnicity significantly impact stroke risk, with certain populations experiencing disproportionately higher rates of stroke and stroke-related mortality 1, 2.
Genetic factors contribute substantially to stroke risk, with monozygotic twins showing nearly 5-fold higher concordance rates compared to dizygotic twins 2. However, genetic screening for primary stroke prevention is not currently recommended due to insufficient evidence 1.
Low birth weight represents an early-life risk factor that cannot be modified in adulthood 1.
Well-Documented Modifiable Risk Factors
Hypertension: The Primary Target
Hypertension affects at least 65 million Americans and is the major modifiable risk factor for both ischemic and hemorrhagic stroke 1. The relationship is continuous, consistent, and independent—for each 10 mmHg increase in blood pressure, stroke risk increases by 30-45% 3.
Antihypertensive therapy reduces stroke risk by 35-44%, with meta-analyses demonstrating a 38% reduction in overall stroke risk and 40% reduction in fatal stroke 1, 3. Both β-blocker therapy (RR 0.71) and diuretic treatment (RR 0.49) are effective 1.
Blood pressure targets should be <140/90 mmHg in the general population, with lower targets for specific subgroups such as patients with diabetes 1, 3.
Cardiac Conditions
Atrial fibrillation is a major cause of cardioembolic strokes, representing one of the most significant cardiac risk factors 2. Patients with atrial fibrillation require specific anticoagulation strategies for stroke prevention.
Presence of atherosclerotic vascular disease in other beds substantially increases stroke risk, with relative risks of 1.73 (95% CI 1.68-1.78) for men and 1.55 (95% CI 1.17-2.07) for women with coronary heart disease, cardiac failure, or symptomatic peripheral arterial disease 1.
Carotid artery stenosis is a significant contributor to stroke risk, particularly when symptomatic or hemodynamically significant 2.
Metabolic Risk Factors
Diabetes mellitus is associated with 9.1% of recurrent strokes and substantially increases first-stroke risk through multiple mechanisms including accelerated atherosclerosis and endothelial dysfunction 1, 2.
Dyslipidemia contributes to atherosclerotic disease and stroke risk, with statin therapy recommended for patients with ischemic stroke who have evidence of atherosclerosis 2.
Sickle cell disease is associated with markedly increased stroke risk, particularly in younger patients 1, 2.
Behavioral and Lifestyle Risk Factors
Cigarette smoking is a major modifiable risk factor, with smoking cessation reducing stroke risk by approximately 38% (HR 0.62,95% CI 0.56-0.68) 4. The benefit of cessation begins immediately and continues to increase over time.
Physical inactivity substantially increases stroke risk, with fewer than 20% of Americans engaging in regular physical activity 5. High leisure-time physical activity reduces atherothrombotic stroke risk (HR 0.89,95% CI 0.80-0.98) 4.
Obesity and adverse body fat distribution increase stroke risk, with obesity accounting for up to 40% of all hypertension cases and 78% in men 1, 5. Central (abdominal) adiposity specifically elevates risk through increased peripheral vascular resistance and insulin resistance 5.
Poor diet quality increases stroke risk, while high diet quality (Mediterranean-style diet with fish, olive oil, grains, fruits, and vegetables) reduces atherothrombotic stroke risk (HR 0.83,95% CI 0.72-0.97) 1, 4.
Alcohol abuse increases stroke risk, though the relationship is complex with moderate consumption potentially having different effects than heavy consumption 1.
Drug abuse is associated with increased stroke risk through multiple mechanisms including vasculopathy and cardioembolism 1.
Hormonal Factors
Postmenopausal hormone therapy increases stroke risk and should not be used for stroke prevention 1.
Oral contraceptive use may increase stroke risk, particularly in older women (1.4- to 2.0-fold increased risk) and those with other risk factors 1, 5.
Less Well-Documented or Potentially Modifiable Risk Factors
The metabolic syndrome represents a cluster of risk factors that collectively increase stroke risk beyond individual components 1.
Sleep-disordered breathing, particularly obstructive sleep apnea, is increasingly recognized as a stroke risk factor and should be assessed in patients with resistant hypertension 1, 5.
Migraine headache, particularly with aura, may be associated with increased stroke risk in certain populations 1.
Hyperhomocysteinemia, elevated lipoprotein(a), and elevated lipoprotein-associated phospholipase represent emerging biochemical markers, though interventions targeting these factors have not consistently shown benefit 1.
Hypercoagulability, inflammation, and infection represent additional areas of investigation, with inflammatory disorders and periodontal disease potentially contributing to stroke risk 1, 6, 7.
Environmental and Socioeconomic Factors
Lower education and poor socioeconomic status serve as surrogates for exposure to traditional high-risk behaviors including smoking, poor nutrition, and lack of preventive medical care 7.
Environmental pollution and passive smoking represent modifiable environmental exposures that increase stroke risk 7.
Depression, stress, and affective disorders have been identified as potential stroke risk factors requiring further investigation 7.
Critical Clinical Approach
Modifiable risk factors account for approximately 90% of the population-attributable risk for stroke 2. This means that aggressive modification of these factors has the potential to prevent the vast majority of strokes.
Targeting multiple risk factors has additive benefits, with comprehensive lifestyle modifications combined with appropriate pharmacological therapy potentially reducing recurrent stroke risk by up to 80% 2.
Risk assessment should be part of routine evaluation for all patients, using tools such as the Framingham Stroke Risk Profile to identify high-risk individuals who could benefit most from interventions 2.
Common Pitfalls to Avoid
Do not underestimate the importance of blood pressure control—even modest reductions in blood pressure translate to substantial reductions in stroke risk, and more than two-thirds of persons over 65 years are hypertensive 1.
Do not overlook atrial fibrillation screening, particularly in older patients, as this represents one of the most treatable causes of cardioembolic stroke 2.
Do not neglect lifestyle modification counseling—smoking cessation, dietary improvement, and increased physical activity are effective interventions that also reduce risk of other cardiovascular diseases 6, 4.
Do not ignore the cumulative effect of multiple risk factors—patients with several modifiable risk factors require aggressive, comprehensive intervention rather than piecemeal management 2, 6.