Citations

Background— Effects were compared in patients in the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial of 2 mechanistically different strategies for treatment of hyperglycemia, insulin-sensitizing and insulin-providing strategies, on biomarker profiles reflecting the balance between fibrinolysis and thrombosis and the intensity of inflammation implicated in diabetic vasculopathy. Methods and Results— A total of 2368 patients with type 2 diabetes mellitus and clinically stable, angiographically documented coronary artery disease were randomized to treatment with 1 of the 2 strategies and followed for an average of 5 years. Plasminogen activator inhibitor type 1 antigen and activity, tissue plasminogen activator antigen, fibrinogen, D-dimer, C-reactive protein, insulin, and hemoglobin A 1c were assayed in blood samples acquired at baseline and at 12 regular intervals throughout the follow-up interval. Higher baseline D-dimer, fibrinogen, and C-reactive protein portended a poor prognosis in patients in both groups. In contrast to the insulin-providing strategy, the insulin-sensitizing strategy led to (1) lower plasma insulin; (2) lower plasminogen activator inhibitor type 1 antigen and activity and lower tissue plasminogen activator antigen (known to track with plasminogen activator inhibitor type 1); and (3) lower C-reactive protein and fibrinogen at all intervals after baseline ( P <0.001 for each). Conclusions— The insulin-sensitizing treatment strategy led to changes in biomarker profiles indicative of decreased insulin resistance, an altered balance between thrombosis and fibrinolysis favoring fibrinolysis, and diminished intensity of the systemic inflammatory state, factors that have been associated with cardiovascular risk. Clinical Trial Registration— http://www.clinicaltrials.gov . Unique identifier: NCT00006305.

To evaluate the short-term results of percutaneous aortic balloon valvuloplasty, 55 consecutive elderly patients with symptomatic, severe aortic stenosis who were at high risk for surgical intervention underwent the procedure, with follow-up by clinical evaluation and Doppler echocardiography. Over a mean follow-up of 6.2 months, there were three early deaths (less than 30 days) and eight late deaths. Nine patients underwent subsequent aortic valve surgery, and four had repeat balloon valvuloplasty. Doppler echocardiography revealed a reduction in aortic valve mean gradient from 48 +/- 18 to 33 +/- 12 mm Hg after the procedure (p less than 0.0001) but a return to 46 +/- 16 mm Hg at follow-up (p less than 0.05). The aortic valve area increased from 0.54 +/- 0.15 to 0.85 +/- 0.23 cm2 after the procedure (p less than 0.0001), but there was a significant decrease to 0.67 +/- 0.19 cm2 at follow-up (p less than 0.05). Of patients free of aortic valve operation or death after 30 days after the procedure, 76% were severely symptomatic before the procedure as compared with 38% at follow-up. In patients undergoing percutaneous aortic balloon valvuloplasty, there is a continued high short-term mortality and a significant incidence of restenosis over short-term follow-up. Nonetheless, a subset of patients do experience sustained clinical improvement from this procedure.

Background and Purpose —Case-control, cohort, and twin studies support a genetic contribution to ischemic stroke risk. Sibling pair linkage methods require identification of concordant or discordant siblings or both. We designed and tested a structured telephone interview to verify the stroke-free phenotype. Methods —A coordinator unaware of medical record data used an 8-item questionnaire to conduct a structured telephone interview of 70 outpatients aged >60 years. The questionnaire inquired about the sudden onset of deficits in strength, sensation, vision, and language. A subject was defined as stroke free by interview if responses to all items on the questionnaire were negative. Results of the telephone interview were compared with data obtained from a systematic medical record review (benchmark). Results —Interview time was 5 minutes or less for all subjects. All subjects who began the interview completed it. Records were reviewed in all subjects. Medical record review detected ischemic stroke or transient ischemic attack (TIA), or both, in 5 patients (7%). There were no significant differences in sex distribution or risk factor rates in patients who were designated stroke free or not stroke free by interview. Having 1 or more positive items on the questionnaire was significantly associated with finding stroke ( P <0.001), TIA ( P <0.001), or either stroke or TIA ( P <0.001), on medical record review. The telephone interview had a sensitivity of 1.0 (95% CI 0.48 to 1.0), specificity of 0.86 (95% CI 0.75 to 0.93), positive predictive value of 0.36 (95% CI 0.13 to 0.65), and negative predictive value of 1.0 (95% CI 0.94 to 1.0). Conclusions —Our instrument can identify the stroke-free individual with a high degree of confidence in a very efficient manner. It may be particularly suited for centralized verification of stroke discordancy in multicentered sib-pair genetic studies.

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.

Background and Purpose CGS 19755 is a competitive N -methyl- d -aspartate (NMDA) receptor antagonist that limits neuronal damage in animal stroke models. The objectives of this multicenter (7 centers), randomized, double-blind, placebo-controlled, ascending-dose phase IIa study were to evaluate the safety and tolerability of CGS 19755 and obtain pharmacokinetic and preliminary data on its efficacious dose range in patients treated within 12 hours of hemispheric ischemic stroke. Methods At each dose level, 6 patients were randomized to one or two intravenous bolus doses of CGS 19755, and 2 patients were randomized to placebo. An unblinded safety and monitoring committee evaluated results at each dose before ascending to the next level. All patients at the first level (1 mg/kg) received two doses separated by 12 hours. The first 2 patients at 2 mg/kg received two doses, but adverse experiences occurred in both; subsequent patient groups received single doses of 2.0, 1.75, or 1.5 mg/kg. Results Adverse experiences (agitation, hallucinations, confusion, paranoia, and delirium) occurred in all 6 patients treated with 2 mg/kg, and in 3 of 5 at 1.75 mg/kg. Similar but milder adverse experiences were noted in 4 of 7 patients at 1.5 mg/kg and 1 of 6 patients at 1.0 mg/kg. Adverse experiences began between 20 minutes and 22 hours (mean, 8 hours) after treatment and lasted 2 to 60 hours (mean, 24 hours). Mortality was 1 of 8 in patients receiving placebo and 3 of 24 in treated patients. In treated survivors, median and mean percent improvement in National Institutes of Health Stroke Scale scores from baseline to terminal visit (mean, 86 days) was comparable at all doses, and 95% of treated patients had Barthel Index scores of ≥70 at the terminal visit. Conclusions We conclude that a single intravenous dose of 1.5 mg/kg CGS 19755 is safe and tolerable in patients with acute ischemic stroke. An efficacy trial is indicated.

Background and Purpose The purpose of this study was to clarify whether mitral valve prolapse increases the subsequent risk of stroke. Methods A historical cohort study was conducted on 1079 residents of Olmsted County, Minnesota, who had an initial echocardiographic diagnosis of mitral valve prolapse between 1975 and 1989 without prior stroke or transient ischemic attack and who were followed up for first stroke occurrence. Results There was an overall twofold increase in the incidence of stroke among individuals with mitral valve prolapse relative to the reference population (standardized morbidity ratio, 2.1; 95% confidence interval, 1.3 to 3.2). Sex, duration of follow-up from the diagnosis of mitral valve prolapse, or calendar year of initial diagnosis did not modify the association. Within the cohort of patients who were at least 35 years old at diagnosis of mitral valve prolapse, a time-dependent proportional-hazards multivariate model and a person-years analysis revealed that age, ischemic heart disease, congestive heart failure, and diabetes mellitus were important determinants for stroke when person-years of observation after mitral valve replacement were excluded. Among seven persons with mitral valve replacement, three strokes occurred in 24 person-years of follow-up. For those with an auscultatory diagnosis of mitral valve prolapse only as the indication for echocardiography (44%), the risk of stroke relative to the population was 1.0 (95% confidence interval, 0.2 to 2.9); for those with another cardiac diagnosis, the standardized morbidity ratio was 2.5 (95% confidence interval, 1.5 to 4.0). Conclusions Individuals with uncomplicated mitral valve prolapse did not have an increased risk of stroke, although a small increase in the risk may not have been detected.

Unruptured intracranial aneurysms constitute a significant public health problem that has not been quantified. The purpose of this study is to document the magnitude of this problem in the United States. National Hospital Discharge Survey data from 1979, 1984, and 1989 served as the basis for calculating patient numbers and frequency distributions. Cost estimates included the direct costs of hospitalization and surgery for those who had surgery, disability and lost income from morbidity, and lost income from mortality. The estimated lifetime cost (including hospitalization, surgery, morbidity, and mortality) for annual cases of patients hospitalized with unruptured intracranial aneurysms in the United States is $522,500,000 compared with $1,755,600,000 for patients with aneurysmal subarachnoid hemorrhage. These data underscore the need to better understand unruptured intracranial aneurysm as a risk factor for subarachnoid hemorrhage, to define other subarachnoid hemorrhage risk factors, and to optimize the management of patients with these conditions.

The purposes of this study were to determine the trend in stroke recurrence over time and the effect of the prestroke blood pressure and management of hypertension on stroke recurrence in 1,680 incidence cases of stroke in residents of Rochester, Minnesota. Recurrent, primarily ischemic, stroke occurred in 267 cases. Stroke recurrence rates did not change during the 30-year period 1950-1979, in contrast to the decline in initial stroke incidence rates during this time. The overall stroke recurrence rates were less than 5%/yr, with cumulative rates of 5.7%, 19.3%, and 28.8% at 1, 5, and 10 years, respectively. Neither level of blood pressure before the first stroke nor management of hypertension had any apparent effect on stroke recurrence rates throughout the follow-up.

Background— The Carotid Revascularization Endarterectomy Versus Stenting Trial (CREST) found a higher risk of stroke after carotid artery stenting and a higher risk of myocardial infarction (MI) after carotid endarterectomy. Methods and Results— Cardiac biomarkers and ECGs were performed before and 6 to 8 hours after either procedure and if there was clinical evidence of ischemia. In CREST, MI was defined as biomarker elevation plus either chest pain or ECG evidence of ischemia. An additional category of biomarker elevation with neither chest pain nor ECG abnormality was prespecified (biomarker+ only). Crude mortality and risk-adjusted mortality for MI and biomarker+ only were assessed during follow-up. Among 2502 patients, 14 MIs occurred in carotid artery stenting and 28 MIs in carotid endarterectomy (hazard ratio, 0.50; 95% confidence interval, 0.26 to 0.94; P =0.032) with a median biomarker ratio of 40 times the upper limit of normal. An additional 8 carotid artery stenting and 12 carotid endarterectomy patients had biomarker+ only (hazard ratio, 0.66; 95% confidence interval, 0.27 to 1.61; P =0.36), and their median biomarker ratio was 14 times the upper limit of normal. Compared with patients without biomarker elevation, mortality was higher over 4 years for those with MI (hazard ratio, 3.40; 95% confidence interval, 1.67 to 6.92) or biomarker+ only (hazard ratio, 3.57; 95% confidence interval, 1.46 to 8.68). After adjustment for baseline risk factors, both MI and biomarker+ only remained independently associated with increased mortality. Conclusions— In patients randomized to carotid endarterectomy versus carotid artery stenting, both MI and biomarker+ only were more common with carotid endarterectomy. Although the levels of biomarker elevation were modest, both events were independently associated with increased future mortality and remain an important consideration in choosing the mode of carotid revascularization or medical therapy. Clinical Trial Registration— URL: http://www.ClinicalTrials.gov . Unique identifier: NCT00004732.

Background— Outcome data for patients receiving implantable cardioverter-defibrillator (ICD) and cardiac resynchronization therapy–defibrillator (CRT-D) devices treated outside of clinical trials are lacking. No clinical trial has evaluated mortality after device implantation or after shock therapy in large numbers of patients with implanted devices that regularly transmit device data over a network. Methods and Results— Survival status in patients implanted with ICD and CRT devices across the United States from a single manufacturer was assessed. Outcomes were compared between patients followed in device clinic settings and those who regularly transmit remote data collected from the device an average of 4 times monthly. Shock delivery and electrogram analysis could be ascertained from patients followed on the network, enabling survival after ICD shock to be evaluated. One- and 5-year survival rates in 185 778 patients after ICD implantation were 92% and 68% and were 88% and 54% for CRT-D device recipients. In 8228 patients implanted with CRT-only devices, survival was 82% and 48% at 1 and 5 years, respectively. For the 69 556 ICD and CRT-D patients receiving remote follow-up on the network, 1- and 5-year survival rates were higher compared with those in the 116 222 patients who received device follow-up in device clinics only (50% reduction; P <0.0001). There were no differences between patients followed on or off the remote network for the characteristics of age, gender, implanted device year or type, and economic or educational status. Shock therapy was associated with subsequent mortality risk for both ICD and CRT-D recipients. Conclusions— Survival after ICD and CRT-D implantation in patients treated in naturalistic practice compares favorably with survival rates observed in clinical trials. Remote follow-up of device data is associated with excellent survival, but arrhythmias that result in device therapy in this population are associated with a higher mortality risk compared with patients who do not require shock therapy.