This is an area of major public health importance in that several modifiable factors are known to increase the liability to stroke. The most important of these are hypertension, atrial fibrillation, diabetes mellitus, cigarette smoking, and hyperlipidemia. Others, such as systemic diseases associated with a hypercoagulable state and the use of contraceptives, also contribute, but only in special circumstances. Hypertension is also the most readily recognized factor in the genesis of primary intracerebral hemorrhage. It appears that the stroke-producing potential of hypertension is as much the product of heightened systolic pressure, as of diastolic pressure (Rabkin et al). The cooperative studies of the Veterans Administration (see Freis et al) and the report by Collins and associates (collating 14 randomized trials of antihypertensive drugs) convincingly demonstrated that the long-term control of hypertension decreased the incidence of both ischemic infarction and intracerebral hemorrhage. It has been found that simple measures such as the use of hydrochlorothiazide for blood pressure control may be, overall, the most effective. The presence of congestive heart failure and coronary atherosclerosis also increases the probability of stroke. As for embolic strokes, the most important risk factors are arrhythmias, mostly atrial fibrillation, which increases the incidence of stroke about sixfold. Structural cardiac disease also imparts a risk of stroke and when combined with atrial fibrillation, as was common in the past with rheumatic valvular disease, the stroke risk increased 18-fold over the general population.
Diabetes hastens the atherosclerotic process in both large and small arteries. Weinberger and colleagues and Roehmholdt and coworkers found diabetic patients to be twice as liable to stroke as age-matched nondiabetic groups. The importance of long-duration cigarette smoking in the development of carotid atherosclerosis has long been known and was quantitated by Ingall and colleagues. The interactions between diabetes and hypertension on the one hand, and intracerebral hemorrhage and atherothrombotic infarction on the other, as well as the association of cardiac disease and cerebral embolism, are considered further on in this chapter in relation to each of these categories of cerebrovascular disease. Numerous clinical trials have also shown a marked reduction in stroke incidence with the use of cholesterol-lowering drugs. As in the case of coronary artery disease, the level of low-density lipoprotein (LDL) cholesterol has the most impact on the incidence of stroke but elevated triglycerides may also confer risk. Subsidiary factors, such as low potassium intake and reduced serum levels of potassium, are associated with an increased stroke rate in several studies, including one in which we participated, but the mechanism of this effect is obscure (Green et al); a detrimental effect on blood pressure is possible. Public health measures designed to detect and reduce the aforementioned risk factors offer the most intelligent long-range approach to the prevention of cerebrovascular disease.
Finally, in keeping with the emerging field of genetic risk factors in human disease, several genetic loci have been found that putatively impart a risk of stroke in various populations. One large study, reported by Ikram and associates, has implicated a polymorphism on chromosome 12, encompassing several genes that have putative connections to vascular disease. However, other groups, such the International Stroke Genetics Consortium, were unable to confirm this. It seems likely that more refined definitions of stroke subtypes and careful genotyping of circumscribed populations will be necessary if genetic risk factors for stroke are to be found that are not simply markers for vasculopathy, inducing diseases such as diabetes, hyperlipidemia, and hypertension. There are of course, genetically determined diseases such as sickle cell anemia and Fabry disease that impart a greatly increased risk of stroke.
The Major Causes of Ischemic Stroke