Stroke Risk Factors

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Stroke risk factors are very well understood. Both modifiable and nonmodifiable risk factors are important. The nonmodifiable stroke risk factors are age, ethnicity, and sex. There are several modifiable stroke risk factors, including hypertension, hypotension, diabetes, atrial fibrillation, congestive heart failure, coronary artery disease, smoking, hyperlipidemia, homocysteinemia, obesity, alcohol intake, and sedentary lifestyle. In addition, there are numerous predisposing factors, or stroke etiologies, including genetically inherited hematologic conditions (e.g., sickle cell disease and protein C deficiency), vascular malformation, connective tissue diseases, vasculitis, substance abuse, trauma with arterial dissection, and patent foramen ovale (Table II).

The most important modifiable stroke risk factor, hypertension, is estimated to affect approximately 50 million Americans (23% of the U.S. population), or 44% of Americans at least 65 years of age. Approximately one-third of all strokes directly relate to the impact of hypertension. Hypertension increases the risk of stroke up to 400%; the relative risk of stroke among persons with hypertension is four times higher than that among individuals lacking this risk factor. As many as 246,500 strokes might be prevented by eliminating the adverse impact of hypertension (i.e., 35% of 700,000 annual strokes). The odds that a person with hypertension will die of stroke decreases from 4 at age 50 to 1 by age 90, suggesting that the impact of hypertension declines considerably with age. The prevalence of hypertension among individuals with stroke increases substantially with age, from about 45% at age 50 to 70% at age 70. Thus, if one lives long enough with hypertension, there is a very high probability that one or more strokes will occur, either silently (without the patient's knowledge) or sympto-matically (with evident problems such as paralysis, numbness, and unsteadiness).

The Stroke Belt States Affected
Figure 1 US map showing stroke rates by state. The annual stroke death rates for each state are depicted. Note the "stroke belt'' within the southeastern U.S. (reproduced with permission, © 2000 Heart and Stroke Statistical Update. Copyright American Heart Association).

Table II

Major Causes of Stroke

Cardiogenic stroke Atrial fibrillation Endocarditis Cardiac valve disease Rheumatic heart disease Cardiomyopathy Acute myocardial infarction Cardiac surgery Congestive heart failure Cardiac arrest Patent foramen ovale Extracranial arterial disease and stroke Aortic arch arteriosclerosis Carotid artery arteriosclerosis Vertebral artery arteriosclerosis Carotid artery dissection Vertebral artery dissection Giant cell arteritis Subclavian steal syndrome Fibromuscular dysplasia Intracranial arterial disease and stroke Aneurysm

Arteriovenous malformation Cerebral angiitis (vasculitis) Arteriosclerosis Cerebral amyloid angiopathy Migraine Vasospasm Toxic vasculopathy Extracranial venous disease and stroke Internal jugular vein occlusion Venous thrombosis with paradoxical embolization Intracranial venous disease and stroke Central vein thrombosis Sagittal sinus thrombosis Respiratory disease and stroke Sleep apnea Respiratory arrest

Chronic obstructive pulmonary disease

Myasthenia gravis

Motor neuron disease





(continued )

Neuromuscular blockade Neuropathy Brain stem stroke Cervical spine trauma Seizures Emphysema Pneumonia Pulmonary embolism Poisoning Microvascular disease of the brain Advanced age Chronic hypertension Diabetes mellitus Smoking Hypotension Amyloid angiopathy Hematologic disorders and stroke Leiden factor V mutation Protein C deficiency Protein S deficiency Antithrombin III deficiency

Anticardiolipin/antiphospholipid antibody syndrome Sickle cell anemia SC disease

Polycythemia rubra vera Thrombocytosis Hemophilia Thrombocytopenia Hepatic failure

Disseminated intravascular coagulation Other

Inflammatory conditions Becet's syndrome Moyamoya disease Wegener's granulomatosis Polyarteritis nodosa Lymphomatoid granulomatosis Takayasu's arteritis Systemic lupus erythematosus Scleroderma Rheumatoid arthritis Traumatic

Carotid cavernous fistula Air embolism Fat/marrow embolism


(continued )

Increased intracranial pressure Infection

Herpes zoster Vascular anomalies

Cavernous sinus syndrome Atrial septal aneurysm Cavernous malformations Telangiectasia Venous malformations Neoplastic

Nonbacterial thrombotic endocarditis Atrial myxoma Malignant atrophic papulosis Hypercoagulable states Cryoglobulinemia

Stroke is more common among individuals with diabetes mellitus. When stroke does occur, it is more likely to be fatal among diabetics than among non-diabetics. After controlling for other stroke risk factors, the relative risk of stroke is 1.5-3.0 among diabetics, and the impact is greatest for elderly women. Diabetes affects about one-fifth of the population, and the attributable risk of stroke is about half that of hypertension.

The prevalence of diabetes differs by racial group. For example, the prevalence of physician-diagnosed diabetes in adults aged 20 or older is 5.4 and 4.7% for non-Hispanic white men and women, respectively; for non-Hispanic blacks, the percentages are 7.6 and 9.5 for men and women; for Mexican Americans, the prevalence of diabetes is 8.1% for men and 11.4% for women. Approximately half of American Indian women aged 45-74 have diabetes. Thus, the risk of diabetes is considerably higher among minority populations than among non-Hispanic whites.

Smoking is the leading preventable cause of death in the United States and a major stroke risk factor. The risk of stroke from any cause is 1.5, but the risk of subarachnoid hemorrhage is 10 times greater among smokers than among nonsmokers. The number of cigarettes per day correlates with stroke risk. After smoking cessation, the stroke risk returns to baseline within 2-5 years.

The Honolulu Heart Program study revealed a continuous and progressive increase in coronary heart disease and thromboembolic stroke rates with increasing cholesterol levels. When the highest and lowest quartiles were compared, the relative risk of stroke was 1.4. This study helped to confirm the long-held suspicion that hyperlipidemia is an independent risk factor for stroke. Two large studies examined a lipid-lowering drug (provastatin) compared to placebo and showed a 19-31% reduction in stroke. Given the strong biological plausibility of the relationship, and the beneficial effects of cholesterol reduction on stroke risk, it seems clear that hyperlipidemia is a significant stroke risk factor.

Low blood pressure is also an important modifiable stroke risk factor. If blood pressure is insufficient to maintain blood flow to the brain, stroke will result. Certain vascular territories may be more prone to cerebral ischemia. For example, intracranial arteriosclerosis impairs the brain's ability to regulate CBF and cerebral perfusion pressure downstream from a significant narrowing (i.e., cerebral autoregulation). Chronic hypertension impairs autoregulation and increases the risk of stroke within the microvascula-ture. Hypertensive women seem to be more susceptible than men to stroke and silent stroke as a result of nocturnal blood pressure decline, which has been associated with the accumulation of cerebrovascular damage in many studies. Certain types of antihyper-tensive medications (short-acting calcium channel blockers) are more likely to lead to significant nocturnal blood pressure decline than others. Currently, there is no reliable way to determine whether blood pressure might be low enough to increase stroke risk or to determine whether specific vascular territories might be more sensitive to blood pressure decline than others.

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