George W. Petty

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.

Left atrial volume: important risk marker of incident atrial fibrillation in 1655 older men and women

OBJECTIVE To evaluate the contribution of left atrial (LA) volume in predicting atrial fibrillation (AF). PATIENTS AND METHODS In this retrospective cohort study, a random sample of 2200 adults was identified from all Olmsted County, Minnesota, residents who had undergone transthoracic echocardiographic assessment between 1990 and 1998 and were 65 years of age or older at the time of examination, were in sinus rhythm, and had no history of AF or other atrial arrhythmias, stroke, pacemaker, congenital heart disease, or valve surgery. The LA volume was measured off-line by using a biplane area-length method. Clinical characteristics and the outcome event of incident AF were determined by retrospective review of medical records. Echocardiographic data were retrieved from the laboratory database. From this cohort, 1655 patients in whom LA size data were available were followed from baseline echocardiogram until development of AF or death. The clinical and echocardiographic associations of AF, especially with respect to the role of LA volume in predicting AF, were determined. RESULTS A total of 666 men and 989 women, mean +/- SD age of 75.2 +/- 7.3 years (range, 65-105 years), were followed for a mean +/- SD of 3.97 +/- 2.75 years (range, < 1.00-10.78 years); 189 (11.4%) developed AF. Cox model 5-year cumulative risks of AF by quartiles of LA volume were 3%, 12%, 15%, and 26%, respectively. With Cox proportional hazards multivariate models, logarithmic LA volume was an independent predictor of AF, incremental to clinical risk factors. After adjusting for age, sex, valvular heart disease, and hypertension, a 30% larger LA volume was associated with a 43% greater risk of AF, incremental to history of congestive heart failure (hazard ratio [HR], 1.887; 95% confidence interval [CI], 1.230-2.895; P = .004), myocardial infarction (HR, 1.751; 95% CI, 1.189-2.577; P = .004), and diabetes (HR, 1.734; 95% CI, 1.066-2.819; P = .03). Left atrial volume remained incremental to combined clinical risk factors and M-mode LA dimension for prediction of AF (P < .001). CONCLUSION This study showed that a larger LA volume was associated with a higher risk of AF in older patients. The predictive value of LA volume was incremental to that of clinical risk profile and conventional M-mode LA dimension.

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 prevalence of atrial fibrillation in incident stroke cases and matched population controls in Rochester, Minnesota: Changes over three decades

OBJECTIVES We sought evidence of a change in the prevalence of atrial fibrillation (AF) over a 30-year period among residents of Rochester, Minnesota. BACKGROUND Atrial fibrillation is increasingly encountered in clinical practice, but there is limited data on secular trends of AF over time. METHODS Within a longitudinal case-control study of ischemic stroke, the prevalence of AF and of selected comorbid conditions among incident stroke cases and age- and gender-matched controls between 1960 and 1989 was determined. RESULTS The mean age +/- standard deviation for the 1,871 stroke cases (45% men) and matched controls was 75 +/- 11 years. For cases, age-adjusted estimates of AF prevalence for 1960 to 1969, 1970 to 1979, and 1980 to 1989 were 11%, 13%, and 16%, respectively, for men, and 13%, 16%, and 20% for women. For controls, the rates were 5%, 8%, and 12%, respectively, for men, and 4%, 6%, and 8% for women. Increasing AF prevalence was associated with increasing age (doubling of odds per decade of age in both cases and controls) and calendar time adjusted for age and gender (cases: odds ratio [OR] per 5 years 1.13, 95% confidence interval [CI], 1.05 to 1.22; controls: OR per 5 years 1.24, 95% CI 1.12 to 1.37). The rates of increase with calendar time were significant for cases (p = 0.001) and controls (p < 0.001) and comparable between the genders. CONCLUSIONS The prevalence of AF increased significantly in ischemic stroke patients and their controls from 1960 to 1989 in Rochester, Minnesota, independent of age and gender. The rate of increase did not differ significantly between men and women.

Left Atrial Volume in the Prediction of First Ischemic Stroke in an Elderly Cohort Without Atrial Fibrillation

OBJECTIVE To determine the clinical importance of left atrial (LA) volume in the prediction of first ischemic stroke. PATIENTS AND METHODS This retrospective cohort study included randomly selected residents of Olmsted County, Minnesota, aged 65 years or older, who had undergone transthoracic echocardiography at least once at the Mayo Clinic in Rochester, Minn, between January 1, 1990, and December 31, 1998, were in sinus rhythm, and had no history of stroke, transient ischemic attack, atrial fibrillation, or valvular heart disease. Patients were monitored through medical records for first ischemic stroke or death. RESULTS Of 1554 residents (59% women) aged 75+/-7 years, 92 (6%) had experienced at least 1 ischemic stroke over 4.3+/-2.7 years (incident stroke rate, 1.4 per 100 person-years). Left atrial volume of 32 mL/m2 or greater (hazard ratio [HR], 1.63; confidence interval [CI], 1.08-2.46) was independent of age (HR, 1.04; CI, 1.02-1.07), diabetes (HR, 1.91; CI, 1.07-3.41), myocardial infarction (HR, 1.64; CI, 1.01-2.64), and hyperlipidemia (HR, 1.55; CI, 1.01-2.37) for the prediction of first ischemic stroke. When quartiles of LA dimension were plotted against quartiles of indexed LA volume, a stepwise increase in risk with each quartile increment was evident only for indexed LA volume. Also, an LA volume of 32 mL/m2 or greater was associated with an increased mortality risk (HR, 1.30; CI, 1.09-1.56), independent of age, sex, and stroke status. CONCLUSIONS In our elderly cohort with no prior atrial fibrillation, LA volume was independently predictive of first ischemic stroke, incremental to age, diabetes, myocardial infarction, and hyperlipidemia. It was also an independent predictor of death.

Cause-Specific Mortality After First Cerebral Infarction: A Population-Based Study

Background and Purpose— Mortality after cerebral infarction (CI) has remained unchanged during the past 20 years, despite advances in neurologic care. Key factors affecting survival may be underrecognized. The purpose of this study was to determine the rate and cause of mortality after first CI. Methods— In this case-control, population-based study, all available medical records were reviewed for Rochester (Minnesota) residents with a first CI between 1985 and 1989 to identify morbidities and cause of death. Predictors for mortality were analyzed. Results— First CI was recorded for 444 patients. Survival was 83% at 1 month, 71% at 1 year, and 46% at 5 years. The most frequent causes of death were cardiovascular events (22%), respiratory infection (21%), and initial stroke complications (14%). Recurrent stroke and cancer accounted for 9% and 7.5% of deaths, respectively. In the first month after CI, 51% of deaths were attributed to the initial CI, 22% to respiratory infections, and 12% to cardiovascular events. During the first year, 26% of deaths resulted from respiratory infections and 28% from cardiovascular disease. Mortality was higher among patients than controls for at least 2 years after CI. Age, cardiac comorbid conditions, CI severity, stroke recurrence, seizures, and respiratory and cardiovascular morbidities were independent predictors of death. Conclusions— In the first month after CI, mortality resulted predominantly from neurologic complications. Later mortality remained high because of respiratory and cardiovascular causes. To improve long-term survival after CI, aggressive management of pulmonary and cardiac disease is as important as secondary stroke prevention.

The role of transcranial Doppler in confirming brain death: Sensitivity, specificity, and suggestions for performance and interpretation

We performed transcranial Doppler (TCD) examinations on 54 comatose patients over a 1-year period. Of 49 patients with technically adequate TCD examinations, 23 met criteria for determination of brain death by clinical and EEG criteria (21) or clinical criteria alone (2; EEG not performed). A TCD waveform abnormality, consisting of absent or reversed diastolic flow, or small early systolic spikes, in at least 2 intracranial arteries, occurred in 21 brain-dead patients, but in none of the other patients in coma. With appropriate guidelines for performance and interpretation, TCD could be incorporated into institutional protocols as a rapid and convenient alternative to EEG for confirmation of brain death.

Incidence of Transient Ischemic Attack in Rochester, Minnesota, 1985–1989

BACKGROUND AND PURPOSE There is scant information available on the incidence of transient ischemic attack (TIA) in a defined population. This study defines incidence rates of first TIA and subtypes of TIA during 1985-1989 and compares the incidence to that obtained from a 1960-1972 cohort study. METHODS Medical records of all residents of Rochester with potential diagnosis of TIA during 1985-1989 were screened to determine whether the case met the criteria for TIA. All available data were used to determine the vascular distribution of the TIA. Average annual age- and sex-adjusted incidence rates were calculated for 1985-1989, and results were compared with incidence rates determined in a Rochester-based 1960-1972 cohort study. RESILTS: Two hundred two cases of first TIA or amaurosis fugax occurred among Rochester residents during 1985-1989. The age- and sex-adjusted incidence rate for any TIA was 68/100 000 population. Incidence of amaurosis fugax was 13/100 000; anterior circulation (cerebral) TIA, 38/100 000; and vertebrobasilar distribution TIA, 14/100 000. Rates were similar to those determined from a 1960-1972 cohort study. CONCLUSIONS The incidence rate of TIA is 41% that of stroke incidence. TIA incidence in Rochester, Minn, is higher than has been previously reported for other sites throughout the world. Although comparison with prior time periods is difficult because of ascertainment issues, it appears that there has been no significant change in TIA incidence since the decade of the 1960s or earlier. This suggests that the most common mechanism for TIA (atherosclerosis) has not changed in prevalence, nor have risk factors leading to this mechanism.

Population-Based Study of the Relationship Between Patent Foramen Ovale and Cerebrovascular Ischemic Events

OBJECTIVE To determine whether patent foramen ovale (PFO) is a risk factor for a cryptogenic cerebrovascular ischemic event (CIE). METHODS This case-control study of 1072 residents of Olmsted County, Minnesota, who underwent contrast transesophageal echocardiography between 1993 and 1997 included 519 controls without CIE randomly selected from the population, 262 controls without CIE referred for transesophageal echocardiography because of cardiac disease, 158 cases with incident CIE of obvious cause (noncryptogenic), and 133 cases with incident CIE of uncertain cause (cryptogenic). RESULTS Large PFOs were detected in 108 randomly selected controls (20.8%), 22 referred controls (8.4%), 17 noncryptogenic CIE cases (10.8%), and 22 cryptogenic CIE cases (16.5%). After adjustment for age, sex, hypertension, smoking, atrial fibrillation, ischemic heart disease, and number of contrast injections, the presence of a large PFO was not significantly associated with group status (P=.07). Using the odds of the presence of large PFO in the randomly selected controls as the reference, the odds ratio (95% confidence interval) of the presence of large PFO was 0.47 (0.26-0.87) for referred controls, 0.69 (0.37-1.29) for noncryptogenic CIE cases, and 1.10 (0.63-1.90) for cryptogenic CIE cases. CONCLUSIONS Patent foramen ovale is not a risk factor for cryptogenic ischemic stroke or transient ischemic attack in the general population. The PFOs importance in the genesis of cryptogenic CIE may have been overestimated in previous studies because of selective referral of cases and underascertainment of PFO among comparison groups of patients referred for echocardiography for clinical indications other than cryptogenic CIE.