Epidemiology

10.1055/b-0034-80405

Epidemiology

Bell, Rodney D., Dechant, Valerie

Pearls

Stroke is the third leading cause of death and the leading cause of disability in the United States.1
Risk factors for stroke include nonmodifiable factors such as age and gender and modifiable factors such as hypertension, diabetes, and smoking.
Awareness of stroke risk factors facilitates stratification of patient stroke risk as well as therapy aimed at improving modifiable risks.

♦ Stroke Incidence

Despite the modern advances in the diagnosis and treatment of cerebrovascular disease, stroke remains an important cause of mortality and morbidity worldwide. The World Health Organization (WHO) estimates that there are 15 million cases of stroke each year. Of these, 5 million will die from the stroke and 5 million will live with long-term disability.2 Stroke is more prevalent in industrialized nations and is a major health concern in the United States. It is estimated that 795,000 strokes occur annually in the U.S. In 2005 the American Heart Association (AHA) reported 143,579 stroke-related deaths, making stroke the third most common cause of death behind heart disease and cancer.1

♦ Stroke Prevalence

Although the overall stroke incidence is expected to increase with the aging population, the rate of death in stroke patients has been declining with advances in acute treatment and supportive care. Due to improved survival after stroke, there are an estimated 4,700,000 stroke survivors living in the United States; 30 to 50% of them do not regain functional independence. Recurrent stroke is common in this population. In stroke survivors of ages 40 to 69, 15% of men and 17% of women are expected to have a recurrent stroke within 5 years. For those with stroke at age 70 or older, the rate of recurrent stroke increases to 23% for men and 27% for women.1

♦ Frequency of Stroke Subtypes

Ischemic stroke is caused by a lack of blood flow to brain tissue. According to data derived from the Framingham Heart Study, approximately 85% of all strokes are ischemic. Sixty percent of ischemic strokes are atherothrombotic, originating from direct occlusion of either small or large vessels. Embolic strokes are caused by a piece of thrombus that migrates from a distant location, causing an occlusion of a cerebral vessel. Embolic stroke accounts for approximately 25% of ischemic strokes. Hemorrhagic stroke accounts for approximately 13% of all strokes. Eight percent of all strokes are intraparenchymal hemorrhage and 5.4% are subarachnoid hemorrhages (SAHs)3 ( Fig. 1.1 ).

♦ Stroke Risk Factors

Epidemiologic studies have shown that patients with vascular risk factors are at an increased risk of stroke. The Framingham Heart Study prospectively followed a cohort of more than 5000 subjects over several decades. Based on these data, a risk profile was created to predict the likelihood of stroke over a 10-year period. The profile includes age, systolic blood pressure, antihypertensive therapy, diabetes, cigarette smoking, cardiovascular disease, atrial fibrillation, and left ventricular hypertrophy.4 Evaluation for risk factors is essential to assessing a patient’s overall stroke risk.

Some risk factors, such as age and gender, cannot be changed. However, many vascular risk factors can be modified by appropriate medical treatment. Diligent surveillance and treatment of modifiable risk factors can significantly modify a patient’s risk of stroke. A full list of nonmodifiable and modifiable stroke risk factors can be found in Table 1.1 .

**Fig. 1.1** Stroke percentages by subtype, based on data collected by the Framingham Heart Study. ABI, atherothrombotic brain infarction; ICH, intracerebral hemorrhage; SAH, subarachnoid hemorrhage. (From Mohr JP, Choi D, Grotta J, Weir B, Wolf P. Stroke: Pathophysiology, Diagnosis and Management, 4th ed. Churchill Livingstone, 2004.)

Nonmodifiable Risk Factors

Age

The annual incidence of stroke increases with age.1 Data from the Framingham Heart Study’s 55-year follow-up demonstrates that the stroke risk approximately doubles in each decade from ages 35 to 95 (Fig. 1.2).3

Gender

Men have a higher incidence of stroke at young ages. This gender difference narrows with advancing age (Fig. 1.2). For the oldest age group (≥85 years), women have a higher incidence of stroke, probably because women are more likely to live to advanced age. In 2005 women accounted for >60% of all stroke deaths.1

Race

Several cohort studies have assessed the effect of race on stroke risk, including the Northern Manhattan Stroke Study, the Atherosclerosis Risk in Communities Study, and the Greater Cincinnati/Northern Kentucky Stroke Study. There is a racial disparity in stroke risk in the United States, with African Americans having the highest risk, followed by Hispanics and then Caucasians. African Americans have nearly twice the stroke risk of Caucasians. This disparity is particularly prominent in patients under 55 years of age. Asian Americans have a lower risk of ischemic stroke but a higher risk of hemorrhagic stroke. Low levels of high-density lipoprotein (HDL) cholesterol are more common in Asian populations and have been linked to an increased risk of hemorrhagic stroke.1

**Table 1.1** Modifiable and Nonmodifiable Stroke Risk Factors
Nonmodifiable Risk Factors
Age
Gender
Race/ethnicity
Genetics
Modifiable Risk Factors
Hypertension
Diabetes
Cigarette smoking
Dyslipidemia
Physical inactivity
Obesity
Excessive alcohol intake
Atrial fibrillation
Other heart disease
Drug abuse
Obstructive sleep apnea
Previous stroke/transient ischemic attack (TIA)
Hypercoagulable state
Aortic atheroma
Patent foramen ovale
Carotid artery disease

Genetics

Studies of twins and families with stroke suggest a genetic component to stroke risk. A complex interaction between multiple genetic susceptibilities and environment rather than a single gene likely conveys an individual’s vulnerability to stroke. Several gene polymorphisms have been identified that may be related to increased risk of ischemic stroke, intracerebral hemorrhage, and SAH5 ^, 6 (Table 1.2).

**Fig. 1.2** Incidence of atherothrombotic brain infarction by age and gender. (Adapted from data from the Framingham Heart Study as presented in Mohr JP, Choi D, Grotta J, Weir B, Wolf P. Stroke: Pathophysiology, Diagnosis and Management, 4th ed. Churchill Livingstone, 2004, p. 15.)

**Table 1.2** Genes with Polymorphisms Independently Associated with Stroke
Gene	Gene Function
Genes Associated with Atherothrombotic Strokes
MTHFR	Encodes the enzyme methylenetetrahydrofolate reductase which is necessary for the breakdown of homocysteine to methionine. Defects cause homocystinuria.
IPF1	Encodes a transcriptional activator involved in the development of the pancreas and glucose regulation. Linked to early-onset diabetes.
TNFSF4	Encodes for cytokine in the tumor necrosis factor ligand family that mediates adhesion of activated T cells to vascular endothelial cells. Linked to myocardial infarction and systemic lupus erythematosus.
ITGB2	Encodes for an integrin protein involved in cell adhesion.
THBS2	Encodes a thrombospondin protein that mediates cell adhesion and migration.
IL6	Encodes a cytokine produced at sites of inflammation. Dysfunction has been linked to diabetes.
ANXA5	Encodes an anticoagulant protein involved in the coagulation cascade.
MMP12	Encodes a matrix degrading enzyme involved in inflammation. Defects are associated with accelerated atherosclerosis.
Genes Associated with Intracerebral Hemorrhage
IL6	See above.
TNF	Encodes proinflammatory cytokine secreted by macrophages that may have a neuroprotective role.
FBN1	Encodes fibrillin-1, a protein that is part of the extracellular matrix. Dysfunction is linked to connective tissue disorders such as Marfan syndrome.
UCP1	Encodes a mitochondrial uncoupling protein. Dysfunction has been linked to obesity.
LIPC	Encodes a protein involved in lipoprotein uptake. Defects have been linked to diabetes.
CCL5	Encodes a cytokine involved chemoattraction of T cells.
Genes Associated with Subarachnoid Hemorrhage
TNF	See above.
CCL5	See above.
MTHFR	See above.
CAPN10	Encodes a calpain protein that has been associated with non-insulin-dependent diabetes mellitus.
UCP3	Encodes a mitochondrial uncoupling protein thought to protect mitochondria against lipid-induced oxidative stress. Defects have been linked to obesity and type 2 diabetes.
OLR1	Encodes a transcription factor important in fetal development of insulin-producing β cells. Defects are linked to both insulin-dependent and non-insulin-dependent diabetes mellitus.
TGFBR2	Encodes a receptor used in cell signal transduction that influences cell growth and division. It has been implicated as a tumor suppressor. Defects have been linked to connective tissue diseases.
IL10	Encodes a cytokine produced by monocytes and lymphocytes involved in immunoregulation. Defects are linked to Crohn’s disease and rheumatoid arthritis.
Source: Adapted from Yamada Y. Identification of genetic factors and development of genetic risk diagnosis systems for cardiovascular diseases and stroke. Circ J 2006;70:1240-1248. Gene functions are as described in the Online Mendelian Inheritance in Man (OMIM) genetic disorder catalog, www.ncbi.nlm.nih.gov.

Cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common hereditary stroke related syndrome. It is caused by a mutation of the NOTCH3 gene that phenotypically results in migraine, mood changes, and subcortical strokes in young adulthood.

Fabry’s disease is an X-linked recessive condition in which deficiency of β-galactosidase A leads to accumulation of trihexosylceramide in the blood vessels, nervous system, kidneys, and skin. These patients are at an increased risk of stroke and heart attack.

Only gold members can continue reading. Log In or Register to continue