Frequency of atrial septal aneurysms in patients with cerebral ischemic events.

BACKGROUND: Atrial septal aneurysm (ASA) is a putative risk factor for cardioembolism. However, the frequency of ASA in the general population has not been adequately determined. Therefore, the frequency in patients with cerebral ischemic events, compared with the frequency in the general population, is poorly defined. We sought to determine the frequency of ASA in the general population and to compare the frequency of ASA in patients with cerebral ischemic events with the frequency in the general population. METHODS AND RESULTS: The frequency of ASA in the population was determined in 363 subjects, a sample of the participants in the Stroke Prevention: Assessment of Risk in a Community study (control subjects), and was compared with the frequency in 355 age- and sex-matched patients undergoing transesophageal echocardiography in search of a cardiac source of embolism after a focal cerebral ischemic event. The proportion with ASA was 7.9% in patients versus 2.2% in control subjects (P=0.002; odds ratio of ASA, 3.65; 95% CI, 1.64 to 8.13, in patients versus control subjects). Patent foramen ovale (PFO) was detected with contrast injections in 56% of subjects with ASA. The presence of ASA predicted the presence of PFO (odds ratio of PFO, 4.57; 95% CI, 2.18 to 9.57, in subjects with versus those without ASA). In 86% of subjects with ASA and cerebral ischemia, transesophageal echocardiography did not detect an alternative source of cardioembolism other than an associated PFO. CONCLUSIONS: The prevalence of ASA based on this population-based study is 2.2%. The frequency of ASA is relatively higher in patients evaluated with transesophageal echocardiography after a cerebral ischemic event. ASA is frequently associated with PFO, suggesting paradoxical embolism as a mechanism of cardioembolism. In patients with cerebral ischemia and ASA, ASA (with or without PFO) commonly is the only potential cardioembolic source detected with transesophageal echocardiography.

Independent association of high blood pressure and aortic atherosclerosis: A population-based study.

BACKGROUND: Atherosclerosis of the thoracic aorta is associated with stroke. The association between hypertension, a major risk factor for stroke, and aortic atherosclerosis has not been determined in the general population. METHODS AND RESULTS: Transesophageal echocardiography was performed in 581 subjects, a random sample of the Olmsted County (Minnesota) population aged >/=45 years participating in the Stroke Prevention: Assessment of Risk in a Community (SPARC) study. Blood pressure was assessed by multiple office measurements and 24-hour ambulatory blood pressure monitoring. The association between blood pressure variables and aortic atherosclerosis was evaluated by multiple logistic regression, adjusting for other associated variables. Among subjects with atherosclerosis, blood pressure variables associated with complex aortic atherosclerosis (protruding plaques >/=4 mm thick, mobile debris, or ulceration) were determined. Age and smoking history were independently associated with aortic atherosclerosis of any degree (P:

Unruptured intracranial aneurysms: natural history, clinical outcome, and risks of surgical and endovascular treatment.

BACKGROUND: The management of unruptured intracranial aneurysms is controversial. Investigators from the International Study of Unruptured Intracranial Aneurysms aimed to assess the natural history of unruptured intracranial aneurysms and to measure the risk associated with their repair. METHODS: Centres in the USA, Canada, and Europe enrolled patients for prospective assessment of unruptured aneurysms. Investigators recorded the natural history in patients who did not have surgery, and assessed morbidity and mortality associated with repair of unruptured aneurysms by either open surgery or endovascular procedures. FINDINGS: 4060 patients were assessed-1692 did not have aneurysmal repair, 1917 had open surgery, and 451 had endovascular procedures. 5-year cumulative rupture rates for patients who did not have a history of subarachnoid haemorrhage with aneurysms located in internal carotid artery, anterior communicating or anterior cerebral artery, or middle cerebral artery were 0%, 2. 6%, 14 5%, and 40% for aneurysms less than 7 mm, 7-12 mm, 13-24 mm, and 25 mm or greater, respectively, compared with rates of 2 5%, 14 5%, 18 4%, and 50%, respectively, for the same size categories involving posterior circulation and posterior communicating artery aneurysms. These rates were often equalled or exceeded by the risks associated with surgical or endovascular repair of comparable lesions. Patients' age was a strong predictor of surgical outcome, and the size and location of an aneurysm predict both surgical and endovascular outcomes. INTERPRETATION: Many factors are involved in management of patients with unruptured intracranial aneurysms. Site, size, and group specific risks of the natural history should be compared with site, size, and age-specific risks of repair for each patient.

Aortic valve sclerosis and aortic atherosclerosis: different manifestations of the same disease? Insights from a population-based study.

OBJECTIVES: The aim of this study was to examine the association between atherosclerosis risk factors, aortic atherosclerosis and aortic valve abnormalities in the general population. BACKGROUND: Clinical and experimental studies suggest that aortic valve sclerosis (AVS) is a manifestation of the atherosclerotic process. METHODS: Three hundred eighty-one subjects, a sample of the Olmsted County (Minnesota) population, were examined by transthoracic and transesophageal echocardiography. The presence of AVS (thickened valve leaflets), elevated transaortic flow velocities and aortic regurgitation (AR) was determined. The associations between atherosclerosis risk factors, aortic atherosclerosis (imaged by transesophageal echocardiography) and aortic valve abnormalities were examined. RESULTS: Age, male gender, body mass index (odds ratio [OR]: 1.07 per kg/m(2); 95% confidence interval [CI]: 1.02 to 1.12), antihypertensive treatment (OR: 1.93; CI: 1.12 to 3.32) and plasma homocysteine levels (OR: 1.89 per twofold increase; CI: 0.99 to 3.61) were independently associated with an increased risk of AVS. Age, body mass index and pulse pressure (OR: 1.21 per 10 mm Hg; CI: 1.00 to 1.46) were associated with elevated (upper quintile) transaortic velocities, whereas only age was independently associated with AR. Sinotubular junction sclerosis (p = 0.001) and atherosclerosis of the ascending aorta (p = 0.03) were independently associated with AVS and elevated transaortic velocities, respectively. CONCLUSIONS: Atherosclerosis risk factors and proximal aortic atherosclerosis are independently associated with aortic valve abnormalities in the general population. These observations suggest that AVS is an atherosclerosis-like process involving the aortic valve.

Influence of coronary heart disease on morbidity and mortality after carotid endarterectomy: a population-based study in Olmsted County, Minnesota (1970-1988)

To evaluate the prognostic importance of coronary artery disease among patients undergoing carotid endarterectomy, 177 residents of Olmsted County, Minnesota who underwent carotid endarterectomy during the period 1970 through 1988 were followed up to July 1, 1989. Patients were stratified as to the presence (n = 64) or absence (n = 93) of overt coronary artery disease or prior myocardial revascularization (n = 20) at the time of endarterectomy. At 30 days after carotid endarterectomy, there were no significant differences between patients with or without coronary artery disease in the occurrence of death, myocardial infarction or stroke. Kaplan-Meier estimate of 8-year relative survival after carotid endarterectomy (assessed as a percent of survival in age- carotid endarterectomy (assessed as a percent of survival in age- and gender-matched control subjects) was 89% in those without and 75% in those with overt coronary artery disease. Of the 59 total deaths, 29 (49%) had a cardiac cause and 4 (7%) were due to stroke (p less than 0.0001). The cumulative incidence of a cardiac event at 8 years after carotid endarterectomy was greater in those with than in those without overt coronary artery disease (61% vs. 25%, p less than 0.0001). In multivariable analysis, uncorrected coronary artery disease and diabetes were the only independent predictors of subsequent cardiac events, whereas age was the only independent predictor of death. These population-based data suggest that carotid endarterectomy can be safely undertaken in patients with stable coronary artery disease. In long-term follow-up of these patients, coronary rather than cerebral vascular disease is the most frequent cause of morbidity and mortality. Thus, these data lend strong support to the concept of early identification and management of coronary artery disease in patients undergoing carotid endarterectomy.

Hypertension and the brain. The National High Blood Pressure Education Program.

Neurogenic mechanisms are important in the maintenance of most forms of hypertension, yet the brain is highly vulnerable to the deleterious effects of elevated blood pressure. Hypertensive encephalopathy results from a sudden, sustained rise in blood pressure sufficient to exceed the upper limit of cerebral blood flow autoregulation. The cerebral circulation adapts to chronic less severe hypertension but at the expense of changes that predispose to stroke due to arterial occlusion or rupture. Stroke is a generic term for a clinical syndrome that includes focal infarction or hemorrhage in the brain, or subarachnoid hemorrhage. Atherothromboembolism and thrombotic occlusion of lipohyalinotic small-diameter end arteries are the principal causes of cerebral infarction. Microaneurysm rupture is the usual cause of hypertension-associated intracerebral hemorrhage. Rupture of aneurysms on the circle of Willis is the most common cause of nontraumatic subarachnoid hemorrhage. Stroke is a major cause of morbidity and mortality, particularly among persons aged 65 years or older. Treatment of diastolic hypertension reduces the incidence of stroke by about 40%. Treatment of isolated systolic hypertension in persons aged 60 years and older reduces the incidence of stroke by more than one third. Blood pressure management in the setting of acute stroke and the role of antihypertensive therapy in the prevention of multi-infarct dementia require further study.

Lone atrial fibrillation in elderly persons: a marker for cardiovascular risk.

BACKGROUND: The risk of stroke in persons aged 60 years and younger with lone atrial fibrillation (LAF) is no greater than in the general population. The effect of older age on the risk of stroke in persons with LAF is less well established. PARTICIPANTS AND METHODS: The risk of stroke in persons with LAF and without substantial comorbidities was examined in a population-based study at a single institution in Olmsted County, Minnesota, and compared with that in an age- and sex-matched population. The mean age was 74 years (range, 61-97 years). The median duration of follow-up was 9.6 years until death or last follow-up. RESULTS: Of 55 patients, 26 had 31 cardiovascular events during follow-up, occurring a median of 5.1 years after diagnosis (range, 0.7-18 years). Of 11 cerebrovascular events, 6 were transient ischemic attacks and 5 were strokes. The event rates (percentage per person-year) were 0.9% for stroke, 1.1% for transient cerebral ischemia, and 2.6% for myocardial infarction, for a total cardiovascular event rate of 5.0% per person-year. The corresponding rates for the age- and sex-matched control group were 0.2%, 0%, and 1.1%, for a total of 1.3% per person-year. The incidence of total cardiovascular events was significantly greater (P< .01) in those with LAF, although there was no difference in survival. CONCLUSION: Lone atrial fibrillation occurring after age 60 years is a risk marker for a substantial increase in cardiovascular events that warrants consideration for antithrombotic therapy.

Predictors of cerebrovascular events and death among patients with valvular heart disease: A population-based study.

BACKGROUND AND PURPOSE: There is little population-based information on cerebrovascular events and survival among valvular heart disease patients. We used the Kaplan-Meier product-limit method and the Cox proportional hazards model to determine rates and predictors of cerebrovascular events and death among valve disease patients. METHODS: This population-based historical cohort study in Olmsted County, Minnesota, reviewed residents with a first echocardiographic diagnosis of mitral stenosis (n=19), mitral regurgitation (n=528), aortic stenosis (n=140), and aortic regurgitation (n=106) between 1985 and 1992. RESULTS: During 2694 person-years of follow-up, 98 patients developed cerebrovascular events and 356 died. Compared with expected numbers, these observations are significantly elevated, with standardized morbidity ratio of 3.2 (95% CI, 2.6 to 3.8) and 2. 5 (95% CI, 2.2 to 2.7), respectively. Independent predictors of cerebrovascular events were age, atrial fibrillation, and severe aortic stenosis. The risk ratio of severe aortic stenosis was 3.5 (95% CI, 1.4 to 8.6), with atrial fibrillation conferring greater risk at younger age. Predictors of death were age, sex, cerebrovascular events, ischemic heart disease, and congestive heart failure, the greatest risk being among those with both congestive heart failure and cerebrovascular events (risk ratio=8.8; 95% CI, 5. 8 to 13.4). Valve disease type and severity were not independent determinants of death. CONCLUSIONS: The risk of cerebrovascular events and death among patients with valve disease remains high. Age, atrial fibrillation, and severe aortic stenosis are independent predictors of cerebrovascular events, and age, sex, cerebrovascular events, congestive heart failure, and ischemic heart disease are independent predictors of death in these patients.

Detection and control of high blood pressure in the community : Do we need a wake-up call?

At the community level, the effect of national programs in increasing hypertension awareness, prevention, treatment, and control is unclear. This study evaluated the degree of detection and control of high blood pressure in a random population-based sample of Olmsted County, Minnesota, residents >/=45 years old, of whom 636 subjects among 1245 eligible residents agreed to participate. Home interview and home and office measurements of blood pressure were used to estimate awareness, treatment, and control rates for hypertension in the community. Mean blood pressures (+/-SD) were 138/80+/-20/12 mm Hg for men and 137/76+/-23/11 mm Hg for women. The overall prevalence of hypertension was 53%. The percentage of subjects with treated and controlled hypertension was 16.6%. Thirty-nine percent of subjects were unaware of their hypertension. Despite clinical trial evidence of reduced morbidity and mortality with antihypertensive therapy, recently reported national data suggest a leveling-off trend for treatment and control of hypertension. This population-based study supports these observations and suggests that at a community level, hypertension awareness and blood pressure control rates are suboptimal, presumably because of decreased attention to the detection and control of hypertension.

Hemifacial spasm in Rochester and Olmsted County, Minnesota, 1960 to 1984.

The incidence of hemifacial spasm in residents of Olmsted County, Minnesota, was studied by reviewing the medical records of patients residing in the community between 1960 and 1984. The average annual incidence rate was 0.74 per 100,000 in men and 0.81 per 100,000 in women, age-adjusted to the 1970 US white population. The average prevalence rate was 7.4 per 100,000 population in men and 14.5 per 100,000 in women. The incidence and prevalence rates were highest in those from 40 to 79 years of age.

Unilateral visual loss in bright light. An unusual symptom of carotid artery occlusive disease.

Five patients with carotid artery occlusive disease had unilateral visual loss in bright light. All five had reduced retinal artery pressure on the side of the visual loss, and arteriograms showed either an occlusion or a high-grade stenosis of the ipsilateral internal carotid artery. Unilateral visual loss in bright light may indicate ipsilateral carotid artery occlusive disease and may reflect the inability of borderline circulation to sustain the increased retinal metabolic activity associated with exposure to bright light.

Carotid occlusive disease. Effect of bright light on visual evoked response.

Four patients had severe carotid artery occlusive disease associated with ipsilateral visual blurring and exposure to bright light. Attenuation of the visual evoked response was noted after patients were exposed to an artificial source of light for 30 s. No significant abnormality of the visual evoked response was seen in the asymptomatic eyes or in the 16 eyes of eight control subjects, some of whom had carotid artery occlusive disease associated with ipsilateral venous stasis retinopathy. We concluded that ischemia of the macular region is necessary to produce these visual symptoms and that local retinal blood flow has been reduced to the flow threshold of electrical failure. These findings provide objective documentation of an abnormality that may be associated with an important symptom indicative of severe carotid artery occlusive disease.

Tuberous sclerosis complex in Olmsted County, Minnesota, 1950-1989.

The incidence of tuberous sclerosis complex in Olmsted County, Minnesota, was 0.28 per 100,000 person-years from 1950 through 1989, the point prevalence on December 31, 1989, was 6.9 per 100,000 persons, and the incidence at birth was 6.0 per 100,000 live births. The incidence was 0.13 per 100,000 person-years from 1950 through 1974 and 0.46 per 100,000 person-years from 1975 through 1989. The higher rate of diagnosis during the later period is believed to be due to the use of computed tomography. Of the 12 patients considered in this study, one patient presented with seizures and severe intellectual disability, six patients presented with seizures, three patients presented with multiple facial angiofibroma, and two patients were asymptomatic.

Aneurysmal subarachnoid hemorrhage and viral infection. Lack of association.

We tested the hypothesis that intracranial aneurysm develops because of viral infection that produces arterial damage, and that aneurysmal rupture is related to viral infection. The following viral agents were studied: influenza A, influenza B, and respiratory syncytial viral titers, by the indirect immunofluorescence method, in 29 patients and 29 controls; herpes simplex virus titers, by immunofluorescence, in 31 patients and 31 controls; rubella viral titers (Rubazyme test), in 34 patients and 34 controls; and influenza A and B viral titers, by the complement fixation method, in 54 patients and 54 controls. Patients were selected on the basis of documented aneurysmal subarachnoid hemorrhage. Analysis, with derivation of the chi 2 method, to compare titer levels in patients and controls for each specific viral titer did not reveal positive correlations between the viral titers and aneurysmal subarachnoid hemorrhage.

Patent foramen ovale in patients with cerebral infarction. A transesophageal echocardiographic study.

OBJECTIVES: To determine the frequency of patent foramen ovale (PFO) among various subtypes of cerebral infarction. To determine whether any historical or clinical characteristics predict the presence or absence of PFO in these patients. DESIGN: Comorbidity and infarct subtype study. SETTING: Referral-based study. PATIENTS: One hundred sixteen patients with cerebral infarction consecutively referred for transesophageal echocardiography during a 6-month period. MAIN OUTCOME MEASURES: Infarct subtype classification was made using a clinical and radiographic diagnostic rubric similar to that used by the Stroke Data Bank of the National Institute of Neurological Diseases and Stroke. The frequency of various risk factors and clinical characteristics in patients with and in those without PFO and the frequency of PFO in patients with various infarct subtypes were compared (chi 2 or Fisher exact tests). RESULTS: Patent foramen ovale was detected in 37 patients (32%). Mean age was similar in those with (60 years) and those without (64 years) PFO. Patent foramen ovale was more frequent among men (39%) than women (20%, P = .03). Patients with PFO had a lower frequency of atrial fibrillation, diabetes mellitus, hypertension, and peripheral vascular disease compared with those without PFO. There was no difference in frequency of the following characteristics in patients with PFO compared with those without PFO: pulmonary embolus, chronic obstructive pulmonary disease, pulmonary hypertension, peripheral embolism, prior cerebral infarction, nosocomial cerebral infarction, Valsalva maneuver at the same time of cerebral infarction, recent surgery, or hemorrhagic transformation of cerebral infarction. Patent foramen ovale was found in 22 (40%) of 55 patients with infarcts of uncertain cause and in 15 (25%) of 61 with infarcts of known cause (cardioembolic, 21%; large vessel atherostenosis, 25%; lacune, 40%) (P = .08). When the analysis was restricted to patients who underwent Valsalva maneuver, PFO with right to left or bidirectional shunt was found in 19 (50%) of 38 patients with infarcts of uncertain cause and in 6 (20%) of 30 with infarcts of known cause (P = .01). CONCLUSION: Although PFO was overrepresented in patients with infarcts of uncertain in our and other studies, it has a high frequency among patients with cerebral infarction of all types. The relation between PFO and stroke requires further study.

Predictive value of carotid bruit for carotid atherosclerosis.

To assess the predictive value of carotid bruit for moderate-to-severe carotid atherosclerosis, the results of carotid arteriograms performed on 1004 subjects were correlated with the findings of auscultation of the carotid arteries. Predictive values of carotid bruit for ipsilateral extracranial carotid atherosclerosis were 77% for localized bruits and 74% for diffuse bruits. The predictive values of extracranial carotid bruit for ipsilateral intracranial carotid atherosclerosis were 16% for localized bruits and 18% for diffuse bruits. Assessing both carotid arteries together, the predictive value of carotid bruit for moderate-to-severe atherosclerosis at any extracranial carotid site was 85%, there being no difference whether the bruits were diffuse, localized, bilateral, or unilateral. Diffuse or localized bruits, whether unilateral or bilateral, are equally predictive of moderate-to-severe atherosclerosis in the extracranial carotid artery, but both are poor predictors of intracranial carotid artery disease.

Predictors of intracranial carotid artery atherosclerosis. Duration of cigarette smoking and hypertension are more powerful than serum lipid levels.

The effect of cigarette smoking on intracranial internal carotid artery atherosclerosis (ICAS) was studied by obtaining cigarette smoking histories and data on other potential predictors, including serum lipid estimations, for consecutive patients undergoing carotid arteriography. The duration of cigarette smoking was the most significant independent predictor of the presence of ICAS. Other independently significant predictors of ICAS were hypertension, diabetes mellitus, and current systolic blood pressure. The interaction of diabetes and duration of smoking was a significant negative predictor. In patients for whom serum lipid values were available, lower levels of apolipoprotein A-I were associated with a higher risk of having ICAS. However, the effect of apolipoprotein A-I as a predictor of the presence of ICAS was far outweighted by the effects of duration of smoking and hypertension.

Primary intracerebral hemorrhage: impact of CT on incidence.

From 1975-1979, the incidence of primary intracerebral hemorrhage (PIH) increased in Rochester, MN, when compared with a previously decreasing incidence. Judging from patients with PIH who were alert at diagnosis, we estimated that 24% of the hemorrhages in earlier years had been mislabeled as infarction. The 30-day survival rate increased from 8% in 1945-1974 to 44% in 1975-1979. The incidence rate was about 45% higher in patients receiving anticoagulant treatment than in those who did not. The increased incidence rate and improved survivorship were attributed to more frequent identification of small PIH by CT.

Long-term prognosis after carotid artery occlusion.

One hundred thirty eight patients with angiographically proved carotid artery occlusion and minimal or no neurologic deficit were followed up for an average of 5 years. For patients 35 years old or over, the observed 5-year survival rate on an actuarial basis was 77% compared with an expected rate of 85% in a matched normal population. For patients 35 years old or over, the subsequent stroke rate was 3% per year, and two-thirds of the strokes were ipsilateral to the carotid artery occlusion. The observed stroke rate for all patients 35 years old or over was eight times the expected rate for a matched normal population. The relative risk of stroke was much greater in the younger patients with atherosclerotic carotid artery occlusion than in the older patients.

Nervous system neoplasms and primary malignancies of other sites. The unique association between meningiomas and breast cancer.

To determine whether nervous system neoplasms are associated with primary malignancies elsewhere, we studied the frequency of multiple primary tumous in patients in whom at least one of the primary tumors was within the nervous system. The patients were Conneticut residents with tumors diagnosed between 1935 and 1964. Of 135 patients, 130 had two primary tumors, four had three primary tumors, and one had four primary tumors. Only with multiple primary tumors involving the brain and breast did the number of observed cases significantly exceed the number of expected cases; eight patients who had a meningioma associated with a breast cancer accounted for this excess. Patients with breast cancer presenting with signs or symptoms of an intracranial neoplasm should be carefully evaluated, for the intracranial lesion may be a potentially curable meningioma.