Pioglitazone after Ischemic Stroke or Transient Ischemic Attack.

BACKGROUND: Patients with ischemic stroke or transient ischemic attack (TIA) are at increased risk for future cardiovascular events despite current preventive therapies. The identification of insulin resistance as a risk factor for stroke and myocardial infarction raised the possibility that pioglitazone, which improves insulin sensitivity, might benefit patients with cerebrovascular disease. METHODS: In this multicenter, double-blind trial, we randomly assigned 3876 patients who had had a recent ischemic stroke or TIA to receive either pioglitazone (target dose, 45 mg daily) or placebo. Eligible patients did not have diabetes but were found to have insulin resistance on the basis of a score of more than 3.0 on the homeostasis model assessment of insulin resistance (HOMA-IR) index. The primary outcome was fatal or nonfatal stroke or myocardial infarction. RESULTS: By 4.8 years, a primary outcome had occurred in 175 of 1939 patients (9.0%) in the pioglitazone group and in 228 of 1937 (11.8%) in the placebo group (hazard ratio in the pioglitazone group, 0.76; 95% confidence interval [CI], 0.62 to 0.93; P=0.007). Diabetes developed in 73 patients (3.8%) and 149 patients (7.7%), respectively (hazard ratio, 0.48; 95% CI, 0.33 to 0.69; P<0.001). There was no significant between-group difference in all-cause mortality (hazard ratio, 0.93; 95% CI, 0.73 to 1.17; P=0.52). Pioglitazone was associated with a greater frequency of weight gain exceeding 4.5 kg than was placebo (52.2% vs. 33.7%, P<0.001), edema (35.6% vs. 24.9%, P<0.001), and bone fracture requiring surgery or hospitalization (5.1% vs. 3.2%, P=0.003). CONCLUSIONS: In this trial involving patients without diabetes who had insulin resistance along with a recent history of ischemic stroke or TIA, the risk of stroke or myocardial infarction was lower among patients who received pioglitazone than among those who received placebo. Pioglitazone was also associated with a lower risk of diabetes but with higher risks of weight gain, edema, and fracture. (Funded by the National Institute of Neurological Disorders and Stroke; ClinicalTrials.gov number, NCT00091949.).

Left atrium dilatation and multiple vascular territory strokes.

BACKGROUND: Atrial fibrillation (AF) is a cause of ischemic stroke and is associated with recurrence and with acute multi-vessel territory non lacunar stroke. Many cryptogenic strokes could be secondary to undiagnosed paroxystic AF. As left atrium (LA) dilatation is a risk factor of AF, we sought to determine if moderate or severe LA dilatation was associated with multiple vascular territory infarcts on magnetic resonance imaging (MRI) in patients with acute ischemic stroke without known AF. Normal LA diameter values are ≤4.0 cm for men and ≤3.8 for women. METHODS: Patients who presented at our center between 2006 and 2011 with a diagnosis of acute ischemic stroke (AIS) or transient ischemick attack (TIA) who had a transthoracic echocardiography and a brain MRI were included. Patients with known or de novo AF diagnosed within 3 months of the event were excluded. The main outcome was the presence of acute multi-vessel territory infarct(s) on MRI. RESULTS: 356 patients were included. The mean LA diameter was 37 mm in the control group (normal or mildly dilated LA) and 49 mm in those with moderately to severely enlarged LA (p<0.001). More patients in the LA dilatation group met the main outcome (20% vs 6%; OR 3.89; 95% CI 1.32-11.43; p=0.0014). CONCLUSIONS: LA dilatation (at least moderate) is associated with acute non lacunar multiple vascular territory infarcts on MRI in patients with AIS or TIA without known AF or a confirmed diagnosis of AF. Further studies are necessary to determine if this population might benefit from anticoagulation therapy.

Vascular cognitive impairment: most useful subtests of the Montreal Cognitive Assessment in minor stroke and transient ischemic attack.

BACKGROUND/AIMS: Cognitive impairment is frequent in cerebrovascular disease but often remains undetected. The Montreal Cognitive Assessment (MoCA) has been proposed in this context. Our aim was to evaluate the MoCA and its subtests in cerebrovascular disease. METHODS: We assessed 386 consecutive patients with minor stroke (National Institutes of Health Stroke Score <4) or transient ischemic attack at 3 months. The MoCA and the modified Rankin Scale (mRS) were administered. Computed tomography (CT) scans were assessed for stroke and white matter changes. An unfavorable functional outcome was defined as mRS >1. RESULTS: The prevalence of cognitive impairment (cutoff of 26) was 55% using the MoCA and 13% using the MMSE. In a multivariate analysis, MoCA <26 was associated with the outcome (OR 3.00, CI 1.78-5.03), as were remote lacunar stroke on CT and white matter changes of at least moderate severity. Five subtests (5-word recall, word list generation, trail-making, abstract reasoning and cube copy) formed an optimal short MoCA with 6/10 or less showing a sensitivity of 91% and a specificity of 83%. CONCLUSION: This study extends the utility of the MoCA to milder forms of cerebrovascular disease. The MoCA is associated with the 3-month functional outcome. Five subtests may constitute an optimal brief tool in vascular cognitive impairment.

Troponin elevation predicts atrial fibrillation in patients with stroke or transient ischemic attack.

BACKGROUND: Atrial fibrillation (AF) is a major cause of ischemic stroke. Cardiac troponin (cTnI) is a marker of myocardial damage and may predict arrhythmia. We sought to determine if increased cTnI levels were a predictor of new-onset AF in ischemic stroke or patients with transient ischemic attack (TIA). METHODS: Consecutive patients who presented to Charles-Lemoyne Hospital between October 2006 and November 2010 with a diagnosis of acute ischemic stroke or TIA, without a history of AF, with a baseline measurement of cTnI were included in the study. The primary outcome was new-onset AF on 24-hour Holter measurement within 1 week of admission in patients without AF on the baseline electrocardiogram (ECG). Secondary outcomes included AF on Holter measurement, death, myocardial infarction (MI), and stroke within 3 months. RESULTS: A total of 408 patients were included. Forty-six patients (11.3%) had elevated cTnI levels. These patients were older and had a higher prevalence of coronary artery disease and diabetes. AF on baseline ECG or 24-hour Holter measurement was present in 51 patients (12.5%) and was more frequent among patients with increased cTnI levels compared to patients with normal cTnI levels (34.7% vs 9.7%; P = .004 multivariate analysis). Elevated cTnI levels also predicted the composite outcome of stroke, MI, and death at 3 months (50.0% vs 16.1%; P = .0001). CONCLUSIONS: cTnI elevation predicts new-onset AF on 24-hour Holter measurement in patients with acute ischemic stroke or TIA and may indicate a poorer prognosis and a higher risk of stroke, MI, and death at 3 months.