Meschia, James F.

Background and Purpose— Recombinant Factor VIIa decreases hematoma growth after spontaneous intracerebral hemorrhage (ICH) and rapidly decreases international normalized ratios in patients on warfarin but is also associated with an increased risk for thromboembolic complications. In this study, we assessed the risk of thromboembolic events in patients receiving recombinant Factor VIIa after ICH associated with warfarin treatment. Methods— We reviewed the medical charts, laboratory data, and radiological findings of consecutive patients with anticoagulation-related hemorrhages of the central nervous system who received recombinant Factor VIIa at Mayo Clinic Rochester and Mayo Clinic Florida between 2002 and 2009. The primary end point was the frequency of new thromboembolic events, including myocardial infarction, deep vein thrombosis, ischemic stroke, and pulmonary embolism. Results— We identified 101 patients; 54% had ICH and 30% subdural hematomas. The most common indications for anticoagulation were atrial fibrillation, deep vein thrombosis, and prosthetic valve. Thirteen patients (12.8%) had new thromboembolic events (10 deep vein thromboses and 3 ischemic strokes) within 90 days after recombinant Factor VIIa administration. Eight of these adverse events occurred within 2 weeks of treatment. In patients with ICH, the rate of thromboembolic complications was 5% and all events were venous. Conclusion— The risk of thromboembolic events in patients who received recombinant Factor VIIa for anticoagulation-associated ICH was not higher than that seen in patients treated for spontaneous ICH in the Factor Seven for Acute Hemorrhagic Stroke (FAST) trial. Spontaneous deep vein thrombosis was the most common complication in our series.

Background and Purpose— Warfarin reduces stroke risk by approximately 60% in patients with atrial fibrillation (AF). Differences in awareness and treatment of AF may contribute to racial and geographic disparities in stroke mortality. The objective was to examine predictors of awareness of the diagnosis of AF and treatment with warfarin. Methods— RE asons for G eographic a nd R acial D ifferences in S troke (REGARDS) is a national, population-based, longitudinal study of 30 239 blacks and whites ≥45 years old with oversampling from blacks and the southeastern stroke belt states. Participants were enrolled January 2003 to October 2007. Data were collected using telephone interview, in-home evaluation, and self-administered questionnaires. The main variable of awareness of AF was defined by a positive answer to “Has a doctor or other health professional ever told you that you had atrial fibrillation?” and whether there was evidence of treatment on the basis of an in-home medications inventory. Results— From baseline electrocardiograms, 432 individuals (88 black and 344 white) had AF. Of these, 88% (360 of 409) had at least 1 additional CHADS 2 stroke risk factor and 60% (258 of 432) were aware of their AF. The odds of blacks being aware of their AF were one third that of whites (OR=0.32; 95% CI: 0.20 to 0.52). Among those aware, the odds of blacks being treated with warfarin were only one fourth as great as whites (OR=0.28; 0.13 to 0.60). Conclusion— Blacks were less likely than whites to be aware of having AF or to be treated with warfarin. Potential reasons for the racial disparity in warfarin treatment warrant further investigation.

Rationale Carotid endarterectomy (CEA) and medical therapy were shown superior to medical therapy alone for symptomatic (ge;50%) and asymptomatic (≥60%) stenosis. Carotid angioplasty stenting (CAS) offers a less invasive alternative. Establishing safety, efficacy, and durability of CAS requires rigorous comparison with CEA in symptomatic and asymptomatic patients. Aims The objective is to compare the efficacy of CAS versus CEA in patients with symptomatic (≥50%) or asymptomatic (≥60%) extracranial carotid stenosis. Design The Carotid Revascularization Endarterectomy vs. Stenting Trial (CREST) is a prospective, randomized, parallel, two-arm, multi-center trial with blinded endpoint adjudication. Primary endpoints are analyzed using standard time-to-event statistical modeling with adjustment for major baseline covariates. Primary analysis is on an intent-to-treat basis. Study Outcomes The primary outcome is the occurrence of any stroke, myocardial infarction, or death during a 30-day peri-procedural period, and ipsilateral stroke during follow-up of up to four years. Secondary outcomes include restenosis and health-related quality of life.

Genetic variations have been shown to influence drug metabolism, risk of adverse drug events, and pharmacodynamic responses for many drugs routinely used to treat patients with stroke or at risk for stroke. Examples include clopidogrel, statins, antihypertensive medications, and coumadin. Further validation studies are needed to assess the clinical utility of selecting drugs and doses based on genetic tests. Physicians, pharmaceutical companies, regulatory agencies, and health insurers continue to grapple with how best to translate this burgeoning field into effective individualized medicine.

Background and Purpose— Ischemic stroke (IS) is a multifactorial disorder with strong evidence from twin, family, and animal model studies suggesting a genetic influence on risk and prognosis. Several candidate genes for IS have been proposed, but few have been replicated. We investigated the contribution of 67 candidate genes (369 single nucleotide polymorphisms [SNPs]) on the risk of IS in a North American population of European descent. Methods— Two independent studies were performed. In the first, 342 SNPs from 52 candidate genes were genotyped in 307 IS cases and 324 control subjects. The SNPs significantly associated with IS were tested for replication in another cohort of 583 IS cases and 270 control subjects. In the second study, 212 SNPs from 62 candidate genes were analyzed in 710 IS cases with subtyping available and 3751 control subjects. Results— None of the candidate genes (SNPs) were significantly associated with IS risk independent of known stroke risk factors after correction for multiple hypotheses testing. Conclusion— These results are consistent with previous meta-analyses that demonstrate an absence of genetic association of variants in plausible candidate genes with IS risk. Our study suggests that the effect of the investigated SNPs may be weak or restricted to specific populations or IS subtypes.

Background and Purpose— The field of ischemic stroke genetics is moving beyond candidate gene studies into the realm of genomewide association studies. Such studies have resulted in discoveries in diverse, complex disorders. Methods— The author conducted an informal qualitative review of peer-reviewed medical literature. Results— The power of genomewide association studies to confirm prior associations and establish new ones is illustrated by recent work focusing on type 2 diabetes mellitus. A pilot genomewide association study of ischemic stroke failed to identify a single gene of major effect. Conclusions— Follow-up studies with substantially greater statistical power are essential and are being planned by the Wellcome Trust and others.

Carotid endarterectomy can lead to alterations in baroreceptor sensitivity. Impairment of this sensitivity can in turn lead to volatility of blood pressure (baroreflex failure syndrome—BFS). Rapid elevations in blood pressure can cause hypertensive encephalopathy in a patient with BFS. A patient is presented with hypertensive intra cerebral hemorrhage associated with BFS.