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Biomedical subjects

James F Toole

Publications and source records attributed to James F Toole.

15 recordsLinked to original sources

The changing risk factor profile of participants enrolled in a secondary stroke prevention trial: Vitamin intervention for stroke prevention.

OBJECTIVE: To determine if the stroke risk factor profile of participants in a large, multicenter secondary stroke prevention trial changed over the recruitment period. METHODS: The 3,680 participants in the Vitamin Intervention for Stroke Prevention (VISP) were categorized into four groups by enrollment date. Baseline patient characteristics and stroke risk factors were compared across groups. RESULTS: Hypertension and hypercholesterolemia management improved but prevalence of three major stroke risk factors did not change. Patients enrolled later had better Mini-Mental State and lower NIH Stroke Scale scores, higher multivitamin use, lower prevalence of cortical infarctions, cardiac symptoms and prior stroke, and lower serum creatinine levels. CONCLUSIONS: Those participants enrolled in the later recruitment periods had a different risk factor profile and risk factors were managed differently compared to those enrolled earlier.

Adult↗

Screening for high-grade carotid stenosis using a portable ultrasonography instrument.

BACKGROUND AND PURPOSE: We investigated the diagnostic performance of a brief Power Doppler Imaging (PDI) screening examination for carotid artery stenoses using a newly developed portable instrument. METHODS: A highly experienced sonographer screened in total 152 carotid arteries by either continuous wave (cw) Doppler (n= 50) or a lightweight (2.4 kg) portable duplex device (n= 102) in a prospective study of 76 high-risk patients. The screening protocols included either spectrum analysis and frequency shift measurement in both internal carotid arteries with cw-Doppler or determination of area and diameter ratios in transverse and longitudinal views of both carotid arteries in B-mode and with PDI, but without velocity measurement. Both protocols were evaluated against a complete routine duplex ultrasonography examination. RESULTS: According to the complete examination, stenoses were <50% in 73 of 102 (71.6%), 50-75% in 19 of 102 (18.6%), 75-95% in 7 of 102 (6.9%), and occluded in 3 of 102 (2.9%) arteries (PDI cohort), and <50% in 39 of 50 (78%), 50-75% in 8 of 50 (16%), 75-95% in 2 of 50 (4%), and occluded in 1 of 50 (2%) artery (cw-Doppler cohort). Mean screening time was 8.8 +/- 2.5 minute (PDI) and 9.4 +/- 2.6 minute (cw-Doppler). For stenoses >75%, A(z) values (area under the receiver operating characteristics curve) were 0.897 for area ratios, 0.843 for diameter ratios (PDI protocol) and 1.0 for the cw-Doppler protocol. CONCLUSIONS: The diagnostic performance of the cw-Doppler protocol was superior to the PDI protocol. Nevertheless, both protocols appear suitable as inexpensive screening strategies to identify subjects with >75% stenosis measured by carotid Doppler ultrasound. However, these preliminary data need further verification.

Aged↗

Plasma total homocysteine levels in stroke patients screened for the vitamin intervention for stroke prevention clinical trial in the era of folate fortification.

Folic acid fortification of grain products was mandated in the USA by January 1998 and in Canada by November 1998. It was hypothesized that screening total plasma homocysteine levels adjusted for age, sex, race and country that were drawn in stroke patients for the Vitamin Intervention for Stroke Prevention trial from 1997 to 2001 would be steady when fortification was completed. Samples were grouped by years 1997/1998, 1999 and 2000/2001, and adjusted means were calculated using a general linear regression model. In 2,612 US and 1,059 Canadian patients, levels showed no consistent trend in the USA alone, while Canadian levels declined (p = 0.06 overall, 0.0003 in the oldest age group). US levels were 0.39 micromol/l (95% CI: -0.08, 0.85) lower than in Canada. Neither fasting nor time since stroke affected the results.

Adult↗

Carotid plaque pathology: thrombosis, ulceration, and stroke pathogenesis.

BACKGROUND AND PURPOSE: To determine the relationship between ulceration, thrombus, and calcification of carotid artery atherosclerotic plaques and symptoms of ipsilateral or contralateral stroke. METHODS: We compared microscopic plaque morphology from patients with and without stroke symptoms ipsilateral or contralateral to the plaque. Plaques were characterized for ulceration, thrombus, and calcification. We analyzed plaques from 241 subjects: 170 patients enrolled in the Asymptomatic Carotid Atherosclerosis Study (ACAS) and 71 patients enrolled in the North American Symptomatic Carotid Endarterectomy Trial (NASCET); 128 subjects had no history of stroke symptoms, 80 subjects had ipsilateral symptoms, and 33 had contralateral symptoms. RESULTS: Plaque ulceration was more common in plaques taken from symptomatic patients than those without symptoms (36% versus 14%; P<0.001); frequency of ulceration was similar for plaques associated with ipsilateral (34%) and contralateral (42%) symptoms. Thrombus was most common in plaques taken from patients with both ipsilateral symptoms and ulceration. The extent of calcification was unassociated with stroke symptoms. CONCLUSIONS: Carotid plaque ulceration and thrombosis are more prevalent in symptomatic patients. Ulceration is more common in symptomatic patients regardless of side of carotid symptoms, whereas thrombus is associated with ipsilateral symptoms and plaque ulceration. Preoperative identification of carotid ulceration and thrombus should lead to greater efficacy of stroke prevention by carotid endarterectomy.

Aged↗

Lowering homocysteine in patients with ischemic stroke to prevent recurrent stroke, myocardial infarction, and death: the Vitamin Intervention for Stroke Prevention (VISP) randomized controlled trial.

CONTEXT: In observational studies, elevated plasma total homocysteine levels have been positively associated with ischemic stroke risk. However the utility of homocysteine-lowering therapy to reduce that risk has not been confirmed by randomized trials. OBJECTIVE: To determine whether high doses of folic acid, pyridoxine (vitamin B6), and cobalamin (vitamin B12), given to lower total homocysteine levels, reduce the risk of recurrent stroke over a 2-year period compared with low doses of these vitamins. DESIGN: Double-blind randomized controlled trial (September 1996-May 2003). SETTING AND PARTICIPANTS: 3680 adults with nondisabling cerebral infarction at 56 university-affiliated hospitals, community hospitals, private neurology practices, and Veterans Affairs medical centers across the United States, Canada, and Scotland. INTERVENTIONS: All participants received best medical and surgical care plus a daily multivitamin containing the US Food and Drug Administration's reference daily intakes of other vitamins; patients were randomly assigned to receive once-daily doses of the high-dose formulation (n = 1827), containing 25 mg of pyridoxine, 0.4 mg of cobalamin, and 2.5 mg of folic acid; or the low-dose formulation (n = 1853), containing 200 microg of pyridoxine, 6 microg of cobalamin and 20 microg of folic acid. MAIN OUTCOME MEASURES: Recurrent cerebral infarction (primary outcome); coronary heart disease (CHD) events and death (secondary outcomes). RESULTS: Mean reduction of total homocysteine was 2 micromol/L greater in the high-dose group than in the low-dose group, but there was no treatment effect on any end point. The unadjusted risk ratio for any stroke, CHD event, or death was 1.0 (95% confidence interval [CI], 0.8-1.1), with chances of an event within 2 years of 18.0% in the high-dose group and 18.6% in the low-dose group. The risk of ischemic stroke within 2 years was 9.2% for the high-dose and 8.8% for the low-dose groups (risk ratio, 1.0; 95% CI, 0.8-1.3) (P =.80 by log-rank test of the primary hypothesis of difference in ischemic stroke between treatment groups). There was a persistent and graded association between baseline total homocysteine level and outcomes. A 3- micromol/L lower total homocysteine level was associated with a 10% lower risk of stroke (P =.05), a 26% lower risk of CHD events (P<.001), and a 16% lower risk of death (P =.001) in the low-dose group and a nonsignificantly lower risk in the high-dose group by 2% for stroke, 7% for CHD events, and 7% for death. CONCLUSIONS: In this trial, moderate reduction of total homocysteine after nondisabling cerebral infarction had no effect on vascular outcomes during the 2 years of follow-up. However, the consistent findings of an association of total homocysteine with vascular risk suggests that further exploration of the hypothesis is warranted and longer trials in different populations with elevated total homocysteine may be necessary.

Adult↗

Vitamin intervention for stroke prevention.

Vitamin Intervention for Stroke Prevention (VISP) is designed to determine whether the utilization of folic acid, vitamins B(6) and B(12), in addition to other risk factor reducing measures, have a demonstrable effect on prevention of recurrent stroke. The entry criteria are a first-ever nondisabling stroke, the patient signs informed consent with willingness to participate and randomization to a high- or low-dose vitamin intervention regimen. Case acquisition of 3,688 individuals has been completed, half in the high-dose and the other half in the low-dose intervention arm. Follow-up is in progress and the end results are expected within the year. The Vitamins to Prevent Stroke (VITATOPS) is a parallel study based in Australia with similar goals, and, hopefully, the data from the two will be comparable and supportive.

Aged↗

Changes in plasma homocyst(e)ine in the acute phase after stroke.

BACKGROUND AND PURPOSE: Elevated plasma homocyst(e)ine [H(e)] concentration has been associated with an increased risk of stroke. Although the literature suggests that H(e) increases from the acute to the convalescent phase after a stroke, it is not known whether H(e) changes within the acute period. METHODS: A prospective, multicenter study was conducted to examine changes in H(e) during the 2 weeks after an incident stroke. Blood samples were collected at days 1, 3, 5, 7, and between 10 and 14 days after the stroke. RESULTS: Seventy-six participants (51 men) were enrolled from 9 sites from February 1997 through June 1998. Mean age was 65.6 years, and subjects had at least two H(e) measurements. The estimated mean H(e) level at baseline was 11.3+/-0.5 micromol/L, which increased consistently to a mean of 12.0+/-0.05, 12.4+/-0.5, 13.3+/-0.5, and 13.7+/-0.7 micromol/L at days 3, 5, 7, and 10 to 14, respectively. The magnitude of the change in H(e) was not affected by age, sex, smoking status, alcohol use, history of hypertension or diabetes, or Rankin Scale Score. CONCLUSIONS: ; These data suggest that the clinical interpretation of H(e) after stroke and the eligibility for clinical trials assessing treatment for elevated H(e) levels require an adjustment in time since stroke to properly interpret the observed H(e) levels.

Acute Disease↗

Association between symptoms reported in a population questionnaire and future ischemic stroke: the ARIC study.

The association between computer diagnosis derived from a symptom questionnaire and onset of first hospitalized ischemic stroke during follow-up for up to 11 years has been assessed for 11,804 participants in the Atherosclerosis Risk in Communities Study who had no baseline history of stroke. Of these participants, 578 reported prior positive transient ischemic attack/stroke symptoms, and 265 strokes occurred during the years 1987-1998. Adjusted for age, locale, sex, and race, persons with self-reported baseline symptoms had 2.8 times the hazard rate for incident ischemic stroke of those without symptoms, with 95% confidence interval 1.9-4.1. Greater relative risk was found among younger individuals, women, African-Americans, persons not current smokers, and those with lower white blood cell count.

Algorithms↗