Stroke Risk Factors, Genetics, and Prevention

Abstract

Stroke is a heterogeneous syndrome, and determining risk factors and treatment depends on the specific pathogenesis of stroke. Risk factors for stroke can be categorized as modifiable and nonmodifiable. Age, sex, and race/ethnicity are nonmodifiable risk factors for both ischemic and hemorrhagic stroke, while hypertension, smoking, diet, and physical inactivity are among some of the more commonly reported modifiable risk factors. More recently described risk factors and triggers of stroke include inflammatory disorders, infection, pollution, and cardiac atrial disorders independent of atrial fibrillation. Single-gene disorders may cause rare, hereditary disorders for which stroke is a primary manifestation. Recent research also suggests that common and rare genetic polymorphisms can influence risk of more common causes of stroke, due to both other risk factors and specific stroke mechanisms, such as atrial fibrillation. Genetic factors, particularly those with environmental interactions, may be more modifiable than previously recognized. Stroke prevention has generally focused on modifiable risk factors. Lifestyle and behavioral modification, such as dietary changes or smoking cessation, not only reduces stroke risk, but also reduces the risk of other cardiovascular diseases. Other prevention strategies include identifying and treating medical conditions, such as hypertension and diabetes, that increase stroke risk. Recent research into risk factors and genetics of stroke has not only identified those at risk for stroke but also identified ways to target at-risk populations for stroke prevention.

Keywords: cerebrovascular disorders; epidemiology; risk factors; stroke; transient ischemic attack.

Figure 1

Atrial Substrate Model of Thromboembolic Stroke. The model emphasizes the importance of systemic and atrial substrate in explaining the relationship between atrial fibrillation (AF) and stroke. Systemic vascular risk factors produce an abnormal atrial tissue substrate that in turn causes both AF and thromboembolism. Once AF develops, the dysrhythmia causes atrial structural remodeling, worsening atrial tissue substrate and atrial dysfunction and thereby further increasing the risk of thromboembolism. Concurrently, the systemic risk factors driving this process separately increase stroke risk by driving specific mechanisms of stroke outside the atrium, such as large-artery atherosclerosis, ventricular systolic dysfunction with reduced ejection fraction, and in-situ cerebral small-vessel occlusion. Once stroke occurs, changes in autonomic tone and a post-stroke inflammatory state may transiently increase the risk of AF. (from Kamel H, Okin P, Elkind MSV, Iadecola C. Atrial Fibrillation and Mechanisms of Stroke: Time for a New Model. Stroke 2016;47(3):895-900.)

Figure 2

Levels of stroke prevention in a population

Figure 3

Healthy lifestyle related practices for improved cardiovascular health DASH: Dietary Approaches to Stop Hypertension; AHA: American Heart Association; USDA: United States Department of Agriculture^,