Primary prevention of ischemic stroke: A statement for healthcare professionals from the Stroke Council of the American Heart Association.

Abstract

HomeCirculationVol. 103, No. 1Primary Prevention of Ischemic Stroke Free AccessOtherPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessOtherPDF/EPUBPrimary Prevention of Ischemic Stroke A Statement for Healthcare Professionals From the Stroke Council of the American Heart Association Larry B. Goldstein, Robert Adams, Kyra Becker, Curt D. Furberg, Philip B. Gorelick, George Hademenos, Martha Hill, George Howard, Virginia J. Howard, Bradley Jacobs, Steven R. Levine, Lori Mosca, Ralph L. Sacco, David G. Sherman, Philip A. Wolf, Gregory J. del Zoppo and Members Larry B. GoldsteinLarry B. Goldstein Search for more papers by this author , Robert AdamsRobert Adams Search for more papers by this author , Kyra BeckerKyra Becker Search for more papers by this author , Curt D. FurbergCurt D. Furberg Search for more papers by this author , Philip B. GorelickPhilip B. Gorelick Search for more papers by this author , George HademenosGeorge Hademenos Search for more papers by this author , Martha HillMartha Hill Search for more papers by this author , George HowardGeorge Howard Search for more papers by this author , Virginia J. HowardVirginia J. Howard Search for more papers by this author , Bradley JacobsBradley Jacobs Search for more papers by this author , Steven R. LevineSteven R. Levine Search for more papers by this author , Lori MoscaLori Mosca Search for more papers by this author , Ralph L. SaccoRalph L. Sacco Search for more papers by this author , David G. ShermanDavid G. Sherman Search for more papers by this author , Philip A. WolfPhilip A. Wolf Search for more papers by this author , Gregory J. del ZoppoGregory J. del Zoppo Search for more papers by this author and Members Members Search for more papers by this author Originally published2 Jan 2001https://doi.org/10.1161/01.CIR.103.1.163Circulation. 2001;103:163–182Stroke ranks as the third leading cause of death in the United States. It is now estimated that there are more than 700 000 incident strokes annually and 4.4 million stroke survivors.12 The economic burden of stroke was estimated by the American Heart Association to be $51 billion (direct and indirect costs) in 1999.3 Despite the advent of treatment of selected patients with acute ischemic stroke with tissue plasminogen activator and the promise of other experimental therapies, the best approach to reducing the burden of stroke remains prevention.45 High-risk or stroke-prone individuals can be identified and targeted for specific interventions.6 This is important because epidemiological data suggest a substantial leveling off of prior declines in stroke-related mortality and a possible increase in stroke incidence.78The Stroke Council of the American Heart Association formed an ad hoc writing group to provide a clear and concise overview of the evidence regarding various established and potential stroke risk factors. The writing group was chosen based on expertise in specific subject areas, and it used literature review, reference to previously published guidelines, and expert opinion to summarize existing evidence and formulate recommendations (Table 1).As given in Tables 2 through 4, risk factors or risk markers for a first stroke were classified according to potential for modification (nonmodifiable, modifiable, or potentially modifiable) and strength of evidence (well documented, less well documented).5 The tables give the estimated prevalence, population attributable risk, relative risk, and risk reduction with treatment for each factor when known. Population attributable risk reflects the proportion of ischemic strokes in the population that can be attributed to a particular risk factor and is given by the formula 100×[prevalence(relative risk−1)/prevalence(relative risk−1)+1]).9 Well-documented modifiable risk factors (Table 3) were considered as those with clear, supportive epidemiological evidence in addition to evidence of risk reduction with modification as documented by randomized trials. Less well-documented or potentially modifiable risk factors were those with either less clear epidemiological evidence or without evidence from randomized trials demonstrating a reduction of stroke risk with modification. Gaps in current knowledge are indicated by question marks in the tables.Table 5 summarizes guideline or consensus statement management recommendations where available. Other recommendations are indicated in the text. Based primarily on an individual patient’s risk assessment profile (the Framingham Heart Study risk profile6 is an easy-to-use and valuable tool for identifying persons at risk of stroke) and overall medical condition, interventions involving appropriate lifestyle behavior changes and surgical and pharmacological treatments can be implemented to treat, control, or modify specific risk factors with the goal of reducing the risk of a first stroke.Nonmodifiable Risk FactorsAlthough these factors are nonmodifiable, they identify individuals at highest risk of stroke and those who may benefit from rigorous prevention or treatment of modifiable risk factors.5 (See Table 2.)AgeThe cumulative effects of aging on the cardiovascular system and the progressive nature of stroke risk factors over a prolonged period of time substantially increase stroke risk. The risk of stroke doubles in each successive decade after 55 years of age.810SexStroke is more prevalent in men than in women.8 Overall, men also have higher age-specific stroke incidence rates than women.11 Exceptions are in 35- to 44-year-olds and in those over 85 years of age in whom women have slightly greater age-specific incidence than men.11 However, stroke-related case-fatality rates are higher in women than men. In 1997, females accounted for 60.8% of stroke fatalities.2 Overall, 1 in 6 women will die of stroke, compared with 1 in 25 who will die of breast cancer.12 Circumstances such as oral contraceptive use and pregnancy uniquely contribute to the risk of stroke in women.131415Race/EthnicityBlacks11116 and some Hispanic Americans1617 have high stroke incidence and mortality rates compared with whites. For example, in the Atherosclerosis Risk In Communities (ARIC) study, blacks had a 38% greater incidence of strokes than whites.18 Possible reasons for the high incidence and mortality rate of strokes in blacks include a higher prevalence of hypertension, obesity, and diabetes mellitus within the black population.192021 However, a higher incidence of these other risk factors does not explain all of the excess risk.19 Epidemiological studies have also shown an increase in stroke incidence among self-identified Hispanic populations.222324 Chinese and Japanese populations generally have high stroke incidence rates as well.25Family HistoryBoth paternal and maternal history of stroke may be associated with increased stroke risk.2627 This increased risk could be mediated through a variety of mechanisms, including genetic heritability of stroke risk factors, the inheritance of susceptibility to the effects of such risk factors, familial sharing of cultural/environmental and lifestyle factors, and the interaction between genetic and environmental factors.28 Studies with twins provide strong data suggesting familial inheritance of stroke. Concordance rates for strokes are markedly higher in monozygotic than in dizygotic twins.29 There is a nearly 5-fold increase in stroke prevalence among monozygotic versus dizygotic twins.30Well-Documented Modifiable Risk FactorsSeveral well-documented modifiable risk factors for stroke exist. (See Table 3.)HypertensionHypertension is a major risk factor for both cerebral infarction and intracerebral hemorrhage.31 The incidence of stroke increases in proportion to both systolic and diastolic blood pressures. This relationship is “direct, continuous, and apparently independent.”32 Blood pressure, particularly systolic blood pressure, increases with age.33 Elevated systolic pressure, with or without an accompanying elevation in diastolic pressure, has been shown to increase stroke risk. Isolated systolic hypertension is an important risk factor for stroke in the elderly (systolic blood pressure >160 mm Hg and diastolic blood pressure <90 mm Hg).34There has been compelling evidence for more than 30 years that the control of high blood pressure contributes to the prevention of stroke as well as to the prevention or reduction of other target-organ damage, including congestive heart failure and renal failure.3536 A meta-analysis of 18 long-term randomized trials found that both β-blocker therapy (relative risk 0.71; 95% CI 0.59 to 0.86) and treatment with high-dose diuretics (relative risk 0.49; 95% CI 0.39 to 0.62) were effective in preventing stroke.37 In the past 10 years, the importance of controlling isolated systolic hypertension to prevent stroke in the elderly has been underscored in clinical trials.38 For example, in the Syst-Eur Trial, 4695 patients with isolated systolic hypertension were randomized to active treatment (nitrendipine and possibly enalapril or hydrochlorothiazide to lower systolic blood pressure 20 mm Hg) or to placebo.38 The trial was stopped when stroke reduction reached 42% in the actively treated group. The Systolic Hypertension in the Elderly Program (SHEP) trial demonstrated a 36% reduction in the incidence of total stroke with antihypertensive treatment (chlorthalidone or atenolol).39 Despite extensive education efforts, a significant proportion of the population has undiagnosed or inadequately treated hypertension.344041 This is particularly true in high-risk race/ethnic groups.42RecommendationRegular screening for hypertension (at least every 2 years in adults) and appropriate management, as summarized in the sixth report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure, are recommended (Table 5).34 (Level of Evidence I, Grade A)SmokingActive (current) cigarette smoking has been long recognized as a major risk factor for stroke. Pathophysiological effects of smoking are multifactorial, affecting both the systemic vasculature and blood rheology. Smoking causes reduced blood vessel distensibility and compliance by leading to increased arterial wall stiffness.43 Smoking is also associated with increased fibrinogen levels, increased platelet aggregation, decreased high-density lipoprotein (HDL) cholesterol levels, and increased hematocrit.44A meta-analysis of 22 studies indicates an approximate doubling of the relative risk of cerebral infarction among smokers versus nonsmokers.45 A prospective estimate of a 1.8-fold increase in stroke risk associated with smoking (after control for other stroke risk factors) from the Framingham Heart Study confirms this substantial increase in risk.46 Currently, 25% of adults are active smokers.47 Therefore, ≈18% of strokes are attributable to active cigarette smoking. This estimated population attributable risk is only slightly higher than the estimated 12% population attributable risk associated with active smoking in the Rochester, Minn, population.9To the extent that former smoking may also place individuals at increased risk of stroke, efforts to prevent the initiation of smoking are important to the primary prevention of stroke. The relative risk of stroke among former smokers (compared with nonsmokers) was 1.34 in the Nurses’ Health Study48 and 1.26 in the Physicians’ Health Study.49 Currently, the Centers for Disease Control and Prevention estimate that 23% of the adult population are former smokers,47 implying a population attributable risk for former smoking of 6%. However, the stroke risk associated with former smoking has been shown to substantially decrease with increasing time since cessation. As such, in the Physicians’ Health and Nurses’ Health studies, the 6% population attributable risk estimate is a function of the distribution of time since quitting. The Framingham Heart Study found stroke risk to be at the level of nonsmokers at 5 years from cessation.50 A second study reported that stroke risks disappeared from 2 to 4 years after smoking cessation and that the benefits of cessation were independent of the age at starting and the number of cigarettes smoked per day.48 Wannamethee et al51 concluded that smoking cessation is associated with a considerable and rapid benefit in decreased risk of stroke, particularly in light smokers (<20 cigarettes/d). However, switching to pipe or cigar smoking confers little benefit, emphasizing the need for complete cessation of smoking.51Avoidance of exposure to environmental tobacco smoke may also play a role in the primary prevention of stroke. Nearly 90% of nonsmokers have been shown to have detectable levels of serum cotinine, assumed to be present through exposure to environmental tobacco smoke.52 Because of the high population prevalence of exposure, even a small increase in the relative risk of stroke associated with exposure to environmental tobacco smoke may have a substantial population attributable risk. However, the increase in relative risk may not be small. It has been suggested that exposure to environmental tobacco smoke increases the risk for coronary events from 20% to 70%. An estimated 62 000 coronary heart disease deaths in 1985 were attributable to exposure to environmental tobacco smoke.52Because atherosclerosis can lead to both stroke and coronary heart disease, it is reasonable to suspect environmental tobacco smoke as a cause for some strokes. After adjusting for potential confounders (age, sex, history of hypertension, heart disease, and diabetes), Bonita and colleagues53 found a 1.82-fold increase (95% CI 1.34 to 2.49) in the risk of stroke among nonsmokers and long-term ex-smokers exposed to environmental tobacco smoke. The risk was significant in both men and women. An increase of 1.82 is surprisingly large; however, even a more modest 1.20-fold increase in relative risk (the lower limit of the estimated effect on coronary heart disease) is associated with an estimated population attributable risk of 12% (based on a 67.5% population exposure, calculated as 90% prevalence of exposure in the 75% of the nonsmoking population).In summary, these data suggest that the population attributable risk associated with all forms of exposure to cigarette smoke is substantial, with current smoking contributing to approximately half of the stroke events (population attributable risk of 18% for current smoking, 6% for former smoking, and 12% for exposure to environmental tobacco smoke).RecommendationSmoking cessation for all current smokers is recommended (Table 5).34 (Level of Evidence III, Grade C; note that the evidence level reflects a lack of prospective randomized trials of smokers compared with nonsmokers. However, the data from cohort and epidemiological studies are consistent and overwhelming.)Diabetes, Hyperinsulinemia, and Insulin ResistanceInsulin-dependent diabetics have both an increased susceptibility to atherosclerosis and an increased prevalence of atherogenic risk factors, notably hypertension, obesity, and abnormal blood lipids. A constellation of metabolic risk factors, termed syndrome X, has also been identified in some type 2 diabetics.5455 The main characteristics of syndrome X are hyperinsulinemia and insulin resistance. These result in the secondary features of the syndrome, including hyperglycemia, increased very-low-density lipoprotein cholesterol, decreased HDL cholesterol, and hypertension.Case-control studies of stroke patients and prospective epidemiological studies have confirmed an independent effect of diabetes on ischemic stroke, with an increased relative risk in diabetics ranging from 1.8- to nearly 6-fold. In the United States, from 1976 to 1980, a history of stroke was 2.5 to 4 times more common in diabetics than in persons with normal glucose tolerance. Among Hawaiian Japanese men in the Honolulu Heart Program, those with diabetes had twice the risk of thromboembolic stroke as nondiabetics, an increase in risk that was independent of other factors.56 In the Framingham Heart Study, although the impact of diabetes was greatest on peripheral arterial disease with intermittent claudication, for which the relative risk was increased 4-fold, coronary and cerebral artery territories were also affected. For brain infarction, the impact of glucose intolerance was greater in women than men, reaching significance as an independent contributor only in older women. Overall, persons with glucose intolerance have double the risk of brain infarction compared with nondiabetics.57High blood pressure is common in patients with type 2 diabetes, with a prevalence of 40% to 60% in adults. The combination of hyperglycemia and hypertension has long been believed to increase the frequency of diabetic complications, including stroke. Several recent trials examining stroke and other cardiovascular outcomes compared the benefit of tight control of blood glucose and blood pressure in type 2 diabetics with less stringent management.58 For combined fatal and nonfatal stroke, tight blood pressure control (mean blood pressure achieved 144/82 mm Hg) resulted in a convincing 44% relative risk reduction compared with more liberal control (mean blood pressure achieved 154/87 mm Hg).59 This 44% benefit in stroke risk reduction is above and beyond the ≥20% risk reduction with antihypertensive treatment found in diabetics in SHEP.60 However, improved glycemic control did not produce a significant reduction in stroke incidence over 9 years of follow-up.61The conclusion reached from these studies and in a recent review is that tight control of hypertension in diabetics significantly reduces stroke incidence.62 Current measures to achieve tight glycemic control are less effective for stroke prevention. Nevertheless, intensive therapy to achieve tight control of hyperglycemia with ≥3 doses per day of insulin in patients with recent-onset insulin-dependent (type 1) diabetes mellitus was shown to reduce microvascular complications, nephropathy, and retinopathy, as well as peripheral neuropathy.59The report of the Heart Outcomes Prevention Evaluation (HOPE) study represents an exciting development in prevention of cardiovascular disease. In this placebo-controlled, randomized clinical trial, the addition of the angiotensin-converting enzyme (ACE) ramipril was compared with the current medical regimen of high-risk patients. The substudy of 3577 diabetic patients (of a total population of 9541 participants in the HOPE study) showed a reduction of the primary combined outcome of myocardial infarction, stroke, and cardiovascular death by 25% (95% CI 12% to 36%, P=0.0004) and a reduction of stroke by 33% (95% CI 10% to 50%, P=0.0074).63 This benefit was present even after adjustment for the minor decrease in blood pressure in the ramipril group. There was also a reduction in diabetic complications (overt nephropathy, dialysis, or need for laser therapy).These new reports provide long-sought evidence for stroke prevention in diabetics. Control of hypertension in diabetics and treatment of high-risk diabetic patients with the ACE inhibitor ramipril prevent stroke.RecommendationsCareful control of hypertension in both type 1 and type 2 diabetics is recommended. (Level of Evidence I, Grade A) Glycemic control is recommended to reduce microvascular complications (Table 5).6465Asymptomatic Carotid StenosisIn the Cardiovascular Health Study, carotid stenoses >50% were detected in 7% of the men and 5% of the women ≥65 years of age.66 Similarly, stenoses of ≥50% were detected in 7% of women and 9% of men aged 66 to 93 years in the Framingham cohort.67 Therefore, it seems likely between 7% and 10% of men and between 5% and 7% of women above age 65 have carotid stenoses >50%.Several studies have attempted to identify subgroups of patients with asymptomatic carotid artery stenosis who may be at particularly elevated risk of stroke. The Toronto Asymptomatic Cervical Bruit Study followed a cohort of 500 patients for a mean of 23 months.68 Overall, cerebral ischemic events (transient ischemic attack [TIA] or stroke) were more frequent in patients with severe (>75%) carotid artery stenosis, progressing carotid artery stenosis, or heart disease and in men. A total of 8 patients (1.6%) had an unheralded stroke; however, only 2 (0.4%) were ipsilateral to a high-grade extracranial carotid artery stenosis as demonstrated by Doppler ultrasonography. In another study, 38 asymptomatic patients with >90% stenosis of the internal carotid artery were followed up for a mean period of 48 months.69 Each year, 1.7% of the patients had an unheralded ipsilateral stroke. More recently, the NASCET (North American Symptomatic Carotid Endarterectomy Trial) investigators have retrospectively reviewed their data regarding the risk of stroke in the territory of an asymptomatic carotid artery stenosis contralateral to the side of the symptomatic vessel.7071 The annual risk of stroke was 3.2% (over 5 years of observation) in patients with 60% to 99% stenosis. The average annual risk of ipsilateral stroke increased from 3.0% for those with 60% to 74% stenosis to 3.7% for those with 75% to 94% stenosis and decreased to 2.9% for those with 95% to 99% stenosis, with a rate of 1.9% for those with complete occlusion. Overall, 45% of ipsilateral strokes in patients with asymptomatic stenosis contralateral to a symptomatic stenosis may be attributable to lacunes or cardioembolism, underscoring the need to fully evaluate these patients for other treatable causes of stroke.Taken together, these and other observational studies suggest that the rate of unheralded stroke ipsilateral to a hemodynamically significant extracranial carotid artery stenosis is ≈1% to 2% annually. This represents a significant factor on a population basis. Some studies suggest that the rate of stroke may be higher in those patients with progressing stenosis than in those with stable disease and higher in those with more severe stenosis. As with asymptomatic carotid bruit, an asymptomatic stenosis of the carotid artery is an important indicator of concomitant ischemic cardiac disease.686972There have been 4 published randomized controlled trials that were designed to address the benefit of carotid endarterectomy in patients with asymptomatic carotid artery stenosis. The CASANOVA (Carotid Artery Stenosis with Asymptomatic Narrowing: Operation Versus Aspirin) study was inconclusive.73 The Mayo Clinic Asymptomatic Carotid Endarterectomy (MACE) study included 71 randomized and 87 nonrandomized patients.74 Surgically treated patients were not given aspirin. There were no major strokes or deaths in either group. However, the study was stopped because myocardial infarction occurred in 26% of those in the surgical arm (no aspirin) versus 9% of those in the aspirin-treated medical arm (P=0.002), reflecting the high incidence of concomitant coronary artery disease in patients with asymptomatic carotid artery stenosis.The Veterans Affairs Cooperative Study of carotid endarterectomy for patients with asymptomatic carotid artery stenosis included 444 men followed up for a mean of 48 months.75 Two hundred eleven patients received best medical therapy plus carotid endarterectomy, and 233 received medical therapy alone (including 650 mg of aspirin twice daily). Patients had >50% stenosis of the extracranial carotid artery demonstrated by angiography. Combined perioperative and angiographic risk was 4.7%. There was a 38% risk reduction for the combined end points of ipsilateral TIA, transient monocular blindness, and stroke over 2 years (P<0.001). Although the rate of fatal and nonfatal stroke was reduced in the surgical group (4.7% versus 9.4%, or 1.2% per year versus 2.4% per year), the difference was not significant (P=0.08). However, the study was not powered to detect differences in outcome subgroups.The Asymptomatic Carotid Atherosclerosis Study (ACAS) was a randomized trial investigating the efficacy of carotid endarterectomy in patients with asymptomatic high-grade (>60% diameter reduction) carotid artery stenosis.76 Patients (n=1662) were randomized to surgery plus medical therapy (n=828) or to medical therapy without carotid endarterectomy (n=834). There was a 1.2% risk of angiography-related complications among the 424 patients undergoing postrandomization angiograms and a 2.3% aggregate perioperative stroke risk. The study was halted after a median follow-up of 2.7 years (4465 patient-years) because a significant benefit of surgery was found. The aggregate rate of ipsilateral stroke, any perioperative stroke, or death in surgically treated patients was estimated at 5% over 5 years; in medically treated patients, the corresponding rate was 11% (53% risk reduction, 2% per year event rate reduced to 1% per year; P=0.004). There was no relationship between benefit and the degree of carotid artery stenosis. Women did not benefit (17% nonsignificant risk reduction in women [95% CI −0.96 to 0.65] versus 66% risk reduction in men [95% CI 0.36 to 0.82]), a difference ascribed to a higher rate of perioperative complications in women (3.6% versus 1.7%). Other studies have also noted an increased risk of perioperative complications after endarterectomy in asymptomatic women compared with men.77 However, as with the Veterans Affairs trial, the study was not powered to detect differences among subgroups of patients.It should be noted that the benefit of endarterectomy in the setting of asymptomatic carotid artery stenosis is highly dependent on surgical risk. Yet, most physicians are not aware of the complication rates of the surgeon to whom they refer patients for the operation.7879RecommendationEndarterectomy may be considered in patients with high-grade asymptomatic carotid stenosis performed by a surgeon with <3% morbidity/mortality rate. (Level of Evidence I, Grade A) Careful patient selection, guided by comorbid conditions, life expectancy, and patient preference, as well as other individual factors, including sex, and followed by a thorough discussion of the risks and benefits of the procedure, is required. It is important that patients with asymptomatic carotid artery stenosis be fully evaluated for other treatable causes of stroke. (See Table 5.)Atrial FibrillationAtrial fibrillation is a common arrhythmia and an important risk factor for stroke, with established effective therapy for stroke prevention. The annual risk of stroke in unselected patients with nonvalvular atrial fibrillation is 3% to 5%, with the condition responsible for 50% of thromboembolic strokes.80 It is estimated that approximately two thirds of the strokes that occur in patients with atrial fibrillation are cardioembolic. The median age of patients with atrial fibrillation is 75 years. The Framingham Heart Study noted a dramatic increase in stroke risk associated with atrial fibrillation with advancing age, from 1.5% for those 50 to 59 years of age to 23.5% for those 80 to 89 years of age.81 In addition, atrial fibrillation was associated with an OR for death of 1.5 (95% CI 1.2 to 1.8) in men and 1.9 (95% CI 1.5 to 2.2) in women after adjustment for other risk factors.Five placebo-controlled trials investigating the efficacy of warfarin in the primary prevention of thromboembolic stroke included the Copenhagen Atrial Fibrillation Aspirin and Anticoagulation (AFASAK) trial,82 Boston Area Anticoagulation Trial for Atrial Fibrillation (BAATAF),83 Stroke Prevention in Atrial Fibrillation I (SPAF I),84 Veterans Affairs Stroke Prevention in Atrial Fibrillation trial (SPINAF),85 and the Canadian Atrial Fibrillation Anticoagulation (CAFA) trial.86 The efficacy of aspirin was studied in 2 of these trials (AFASAK and SPAF I). Combined analysis of these 5 trials showed that the relative risk of thromboembolic strokes for patients treated with warfarin was reduced by 68%.An important observation arising from the randomized treatment trials is that there are a limited number of predictors of high stroke risk within the population of patients with atrial fibrillation. The predictors of high risk include advancing age, prior TIA or stroke, systolic hypertension (systolic blood pressure >160 mm Hg), a history of hypertension, impaired left ventricular function, diabetes mellitus, and women over the age of 75 years.87 Long-term oral anticoagulation of patients with these high-risk features reduces the risk of stroke by 68% based on results of the intention-to-treat analysis of the randomized trials and by as much as 80% when the on-treatment effect is noted.88RecommendationAntithrombotic therapy (warfarin or aspirin) should be considered for patients with nonvalvular atrial fibrillation based on an assessment of their risk of embolism and risk of bleeding complications (Tables 4 and 5).87 (Level of Evidence I, Grade A)Other Cardiac DiseaseOther types of cardiac disease that contribute a small yet finite risk to thromboembolic stroke include dilated cardiomyopathy, valvular heart disease (eg, mitral valve prolapse, endocarditis, and prosthetic cardiac valves), and intracardiac congenital defects (eg, patent foramen ovale, atrial septal defect, and atrial septal aneurysm). Overall, an estimated 20% of ischemic strokes are due to cardiogenic embolism. Potential cardiac sources of emboli are associated with up to 40% of cryptogenic strokes in some series involving the younger population.89The presence of cerebrovascular disease is strongly associated with the presence of symptomatic90919293 and asymptomatic9495969798 cardiac disease. Conversely, based on the Framing