Jack P. Whisnant

The natural history of lone atrial fibrillation. A population-based study over three decades

From 1950 to 1980, 3623 patients from Olmsted County, Minnesota, were found to have atrial fibrillation. Ninety-seven of these patients (2.7 percent), who were 60 years old or younger at diagnosis, had lone atrial fibrillation (atrial fibrillation in the absence of overt cardiovascular disease or precipitating illness), and their data were reviewed to determine the incidence of thromboemboli. Twenty of these patients (21 percent) had an isolated episode of atrial fibrillation, 56 (58 percent) had recurrent atrial fibrillation, and 21 (22 percent) had chronic atrial fibrillation. The total follow-up period was 1440 person-years, with a mean of 14.8 years per patient. The mean age at diagnosis was 44 years. Nineteen cardiovascular events occurred in 17 patients; 4 patients had strokes thought to be due to emboli from atrial fibrillation, and 4 had myocardial infarctions without overt evidence of previous coronary artery disease. The probability of survival at 15 years was 94 percent among the patients with lone atrial fibrillation. At 15 years, 1.3 percent of the patients had had a stroke on a cumulative actuarial basis. On an actuarial basis, there was no difference in survival or in survival free of stroke among the patients with the three types of lone atrial fibrillation (i.e., isolated, recurrent, and chronic). We conclude that lone atrial fibrillation in patients under the age of 60 at diagnosis is associated with a very low risk of stroke. This suggests that routine anticoagulation may not be warranted.

Ischemic Stroke Subtypes A Population-Based Study of Functional Outcome, Survival, and Recurrence

BACKGROUND AND PURPOSE There is scant population-based information on functional outcome, survival, and recurrence for ischemic stroke subtypes. METHODS We identified all residents of Rochester, Minnesota, with a first ischemic stroke from 1985 through 1989 using the resources of the Rochester Epidemiology Project medical records linkage system. After reviewing medical records and imaging studies, we assigned patients to 4 major ischemic stroke categories based on National Institute of Neurological Diseases and Stroke Data Bank criteria: large-vessel cervical or intracranial atherosclerosis with stenosis (ATH, n=74), cardioembolic (CE, n=132), lacunar (LAC, n=72), and infarct of uncertain cause (IUC, n=164). We used the Rankin disability score to assess functional outcome and the Kaplan-Meier product-limit method and Cox proportional hazards regression analysis with bootstrap validation to estimate rates and identify predictors of survival and recurrent stroke among these patients. RESULTS Rankin disabilities were different across stroke subtypes at the time of stroke and 3 months and 1 year later (P=0.001). LAC was associated with milder deficits compared with other subtypes. Mean follow-up among the 442 patients in the cohort was 3.2 years. Estimated rates of recurrent stroke at 30 days were significantly different (P<0.001): ATH, 18.5% (95% CI 9.4% to 27.5%); CE, 5.3% (95% CI 1.2% to 9.6%); LAC, 1.4% (95% CI 0.0% to 4.1%); and IUC, 3. 3% (95% CI 0.4% to 6.2%). After adjusting for age, sex, and stroke severity, infarct subtype was an independent determinant of recurrent stroke within 30 days (P=0.0006; eg, risk ratio for ATH compared with CE=3.3, 95% CI 1.2 to 9.3) but not long term (P=0.07). Four of 25 recurrent strokes within 30 days were procedure-related, each in patients with ATH. Five-year death rates were significantly different (P<0.001): ATH, 32.2% (95% CI 21.1% to 43.2%); CE, 80.4% (95% CI 73.1% to 87.6%); LAC, 35.1% (95% CI 23.6% to 46.0%); and IUC, 48.6% (95% CI 40.5% to 56.7%). With adjustment for age, sex, cardiac comorbidity, and stroke severity, the subtype of ischemic stroke was an independent determinant of long-term (P=0.018; eg, risk ratio for ATH compared with cardioembolic=0.47, 95% CI 0.29 to 0.77) but not 30-day survival (P=0.2). CONCLUSIONS Early recurrence rates for ischemic stroke caused by ATH are higher than those for other subtypes and higher than previous non-population-based studies have reported. Some of the increased risk of early recurrence among patients with ATH may be iatrogenic. Patients with LAC have better poststroke functional status than those with other subtypes. Survival is poorest among those with ischemic stroke with a cardiac source of embolism.

Ischemic Stroke Subtypes A Population-Based Study of Incidence and Risk Factors

BACKGROUND AND PURPOSE There is scant population-based information on incidence and risk factors for ischemic stroke subtypes. METHODS We identified all 454 residents of Rochester, Minn, with a first ischemic stroke between 1985 and 1989 from the Rochester Epidemiology Project medical records linkage system. We used Stroke Data Bank criteria to assign infarct subtypes after reviewing medical records and brain imaging. We adjusted average annual incidence rates by age and sex to the US 1990 population and compared the age-adjusted frequency of stroke risk factors across ischemic stroke subtypes. RESULTS Age- and sex-adjusted incidence rates (per 100 000 population) were as follows: large-vessel cervical or intracranial atherosclerosis with >50% stenosis, 27; cardioembolic, 40; lacuna, 25; uncertain cause, 52; other or uncommon cause, 4. Sex differences in incidence rates were detected only for atherosclerosis with stenosis (47 [95% CI, 34 to 61] for men; 12 [95% CI, 7 to 17] for women). There was no difference in prior transient ischemic attack and hypertension among subtypes, and diabetes was not more common among patients with lacunar infarction than other common subtypes. CONCLUSIONS The age-adjusted incidence rate of stroke due to stenosis of the large cervicocephalic vessels is nearly 4 times higher for men than for women. There is no association between preceding transient ischemic attack and stroke mechanism. Diabetes and hypertension are not more common among patients with lacunae. Age- and sex-adjusted incidence rates for ischemic stroke subtypes in this population can be compared with similarly determined rates from other populations.

Dementia after ischemic stroke A population-based study in Rochester, Minnesota (1960-1984)

Article abstract-We used the medical records linkage system for the population of Rochester, Minnesota, to identify persons in the community who had their first cerebral infarct without previous dementia. In this cohort (n = 971), the incidence of dementia in the first year was nine times greater than expected, but if we did not observe dementia in the first year, the risk of dementia in the cohort each year thereafter was about twice the risk in the population. After the first year, a 50% increase was observed in Alzheimers disease in the cohort compared with that in the community. Although the incidence of dementia increased with increasing age, the standardized morbidity ratios decreased with increasing age. Age, sex (male), and second stroke were significant independent predictors of dementia in a multivariate Cox proportional hazards model. There was no effect of location or clinical severity of infarct on the rate of occurrence of dementia. NEUROLOGY 19;: 154-159

Survival and recurrence after first cerebral infarction : A population-based study in Rochester, Minnesota, 1975 through 1989

We used the Kaplan-Meier product limit method to estimate rates and Cox proportional hazards regression analysis with bootstrap validation to model significant independent predictors of and temporal trends in survival and recurrent stroke among 1,111 residents of Rochester, MN, who had a first cerebral infarction from 1975 through 1989. The risk of death after first cerebral infarction was 7% ± 0.7% at 7 days, 14% ± 1.0% at 30 days, 27% ± 1.3% at 1 year, and 53% ± 1.5% at 5 years. Independent risk factors for death after first cerebral infarction were age(p < 0.0001), congestive heart failure (p < 0.0001), persistent atrial fibrillation (p < 0.0001), recurrent stroke (p < 0.0001), and ischemic heart disease (p< 0.0001 for age ≤70, p > 0.05 for age >70). The risk of recurrent stroke after first cerebral infarction was 2% ± 0.4% at 7 days, 4% ± 0.6% at 30 days, 12% ± 1.1% at 1 year, and 29%± 1.7% at 5 years. Age (p = 0.0002) and diabetes mellitus(p = 0.0004) were the only significant independent predictors of recurrent stroke. Neither the year nor the quinquennium of the first cerebral infarction was a significant determinant of survival or recurrence. The temporal trend toward improving survival after first cerebral infarction documented in Rochester, MN, in the decades before 1975 has ended.

The unchanging pattern of subarachnoid hemorrhage in a community

The average annual incidence of subarachnoid hemorrhage (SAH) from aneurysm rupture in Rochester, Minnesota, has remained remarkably constant at about 11 per 100,000 population. Age-specific incidence increased with age. Survival after SAH depended on: (1) clinical grade, (2) time after onset of SAH, and (3) presence of intracerebral hematoma. Among those who survived to receive medical attention, 48% were clinical grade 1 or 2, 20% were grade 3, and 32% were grade 4 or 5. Proved rebleeding occurred within 10 days of the first SAH in 20% of patients who survived until hospital admission.

POPULATION – BASED STUDY OF SEIZURE DISORDERS AFTER CEREBRAL INFARCTION

We performed the first population-based study that determined the magnitude of the risk and identified the factors predictive of developing seizure disorders after cerebral infarction. Five hundred thirty-five consecutive persons without prior unprovoked seizures were followed from their first cerebral infarctions until death or migration out of Rochester, Minnesota. Thirty-three patients (6%) developed early seizures (within 1 week), 78% of which occurred within the first 24 hours after infarction. Using multivariate analysis, the only factor predictive of early seizure occurrence was anterior hemisphere location of infarct (odds ratio 4.0, 95% CI 1.2 to 13.7). Twenty-seven patients developed an initial late seizure (past 1 week), whereas 18 developed epilepsy (recurrent late seizures). Compared with the population in the community, the risk during the first year was 23 times higher for initial late seizures and 17 times higher for epilepsy. The cumulative probability of developing initial late seizures was 3.0% by 1 year, 4.7% by 2 years, 7.4% by 5 years, and 8.9% by 10 years. Independent predictive factors on multivariate analysis for initial late seizures were early seizure occurrence (hazard ratio of 7.8 [95% CI 2.8 to 21.7]) and stroke recurrence (3.1 [1.2 to 8.3]). Both early seizure occurrence (16.4 [5.5 to 49.2]) and stroke recurrence (3.5 [1.2 to 10.5]) independently predicted the development of epilepsy as well. We also found that early seizure occurrence predisposed those with initial late seizures to develop epilepsy. NEUROLOGY 1996; 46 350-355

Incidence rates of stroke in the eighties: the end of the decline in stroke?

Studies of the population of Rochester, Minnesota, have provided the only data on temporal trends for the incidence of stroke in North America. Among the residents of Rochester, the average annual incidence rate of stroke declined by 46%, from 213 to 115 per 100,000 population, between 1950-1954 and 1975-1979. The decline occurred in all age and sex groups, but it occurred earlier in women than in men. The rates stabilized in the 1970s, and did so earlier in women. For 1980-1984, the incidence rate of stroke was 17% higher than that for 1975-1979. The onset of the decline in incidence rates coincided with the introduction of effective antihypertensive therapy, but stabilized and increased rates were associated with continuing improvement in the control of hypertension. The increase in the incidence rates of stroke coincided with the introduction of computed tomography, which appeared to increase the detection of less severe strokes.

Neurologic disease in biopsy‐proven giant cell (temporal) arteritis

Neurologic findings were studied in 166 consecutive patients with biopsy-proven giant cell (temporal) arteritis. Neurologic problems occurred in 51 patients (31%): neuropathies (23), TIA/strokes (12), neuro-otologic syndromes (11), tremor (6), neuropsychiatric syndromes (5), tongue numbness (3), and myelopathy (1). Neuro-ophthalmologic problems occurred in 35 patients (21%): amaurosis fugax (AF) (17), permanent vision loss (PVL) (14), scintillating scotoma (8), and diplopia (3). Abnormalities in large arteries in 52 patients (31%) included bruits and diminished pulses. The carotid artery was involved in 31 patients (bilateral in 58%). Overall, 35% of patients with carotid disease had TIA/stroke, AF, or PVL.

The Natural History of Unruptured Intracranial Aneurysms

This study defines the natural history of a selected group of 65 patients with 81 unruptured intracranial saccular aneurysms who did not undergo surgery. Eight of the 65 patients with aneurysms had intracranial hemorrhage due to aneurysmal rupture over a mean follow-up interval of slightly over eight years. We performed a multivariate discriminant analysis to assess the relation of several independent variables to aneurysmal ruptures. These variables included age, sex, aneurysm size, number of aneurysms, presence of multilobed aneurysms, aneurysmal symptoms other than rupture, aneurysm location, and hypertension at or before the identification of the aneurysm. The only variable of unquestionable significance was aneurysm size, which was noted in 73 instances. None of the 44 aneurysms smaller than 1 cm in diameter ruptured, whereas eight of the 29 aneurysms 1 cm or more in diameter eventually did. We conclude that unruptured intracranial saccular aneurysms smaller than 1 cm in diameter have a very low probability of subsequent rupture.