News from the International Stroke Conference 2006

Kissimmee, Fla—Atherosclerotic burden is an independent predictor of death from a first ischemic stroke, said Jaume Roquer, MD, PhD, at the American Stroke Association’s International Stroke Conference 2006.

Higher atherosclerotic burden predicts higher early stroke mortality

The impact of cumulative vascular risk factors on early mortality after stroke has not been studied; however, many studies have demonstrated that having several vascular risk factors is associated with worse outcomes in ischemic heart disease.

“Atherosclerosis involves, in general, the whole arterial vessel tree, and patients with symptomatic lesions in 1 vascular bed often have additional asymptomatic atherosclerotic lesions in other vascular regions,” said Dr Roquer, a physician at Hospital Del Mar in Barcelona.

“We hypothesize that the atherosclerotic burden is related to an impairment of cerebral vasoregulatory mechanisms facilitating more serious and deleterious strokes.”

A composite atherosclerotic burden score (ABS), from 0 to 2, was derived from histories of ischemic heart disease and peripheral arterial disease. The impact of this score on in-hospital mortality was evaluated in 1450 consecutive first-ever stroke patients, whose diagnosis of cerebral infarction was confirmed by computed tomography or magnetic resonance imaging. All patients were assessed within 24 hours of stroke onset and had several vascular risk factors recorded, including hypertension, diabetes, hyperlipid­emia, atrial fibrillation, ischemic cardiomyopathy, and peripheral arterial disease, and current smoking. The im­pact of the atherosclerotic burden score on mortality was adjusted for these risk factors.

A positive association was observed between ABS and early mortality (P < .001). One hundred seventy-two pa&shy;tients died in the hospital. In-hospital mortality was 10.5% in patients with an ABS score of 0, 15.7% in patients with an ABS score of 1, and 27.9% in patients with an ABS score of 2.

After adjusting for age, gender, vascular risk factors, and stroke severity, ABS remained statistically significant for in-hospital death (P = .0001). Compared with patients having no previous atherosclerotic burden, the risk of in-hospital death increased by 83% (P < .001) in patients with an ABS score of 1, and by 154% (P < .006) in patients with an ABS score of 2.

Other predictors of in-hospital death were age 75 years or older, male gender, atrial fibrillation, stroke severity, and hyperlipidemia.

Clinical predictors of early death in patients suffering an acute ischemic stroke have been studied extensively, with age, atrial fibrillation, and stroke severity being the most powerful clinical predictors. Other factors such as diabetes, hyperglycemia, congestive heart failure, low levels of cholesterol, and low levels of triglycerides have also been described, but their deleterious role is less clear, said Dr Roquer.

“Our study shows that atherosclerotic burden assessed with a composite score using history of ischemic heart disease and peripheral arterial disease is an independent predictor of in-hospital death in a dose-dependent manner,” he said. “It has been reported that the atherosclerotic load, as&shy;sessed by the number of vascular risk factors, has a significant inverse relation with aortic compliance, a sign of artery stiffness, determined by Dop&shy;pler ultrasound.”

Greater artery stiffness induced by atherosclerotic burden is independently related with fatal stroke in patients with essential hypertension, he noted.

Multiple studies confirm the benefit of statins in acute ischemic stroke

Kissimmee, Fla—Studies presented at the American Stroke Associa&shy;tion’s International Stroke Conference 2006 confirm the value of statins in improving outcomes in patients who suffer ischemic stroke.

• Statin pretreatment in patients who suffer a first-ever ischemic stroke halves the risk of stroke progression, reported Atsushi Shiraishi, MD, at Tokyo Medical and Dental University.

He and colleagues evaluated 523 first-ever stroke patients within 48 hours of stroke onset. Stroke progression, defined as a worsening of more than 2 points on the National Institutes of Health Stroke Scale or death, occurred in 7 of 64 (10.9%) patients taking a statin before their stroke, compared with 108 of 459 (23.5%) who did not take statins prior to their stroke (P = .027). After multivariable adjustment, statin pretreatment remained significant in preventing stroke progression (hazard ratio, 0.45; P = .04). The benefit of statin pretreatment appeared greatest in patients with large-artery atherosclerosis, although the sample size was too small to draw definitive conclusions.

They suggest future randomized, controlled trials to assess the utility of statins as acute stroke therapy.

• Patients who used lipid-lowering agents, most often statins, had a reduction in in-hospital mortality and stroke severity following acute ischemic stroke versus patients not using such agents, according to a retrospective chart re&shy;view conducted by Norina Allen, MPH, a doctoral candidate at Yale University, New Haven, Conn.

Charts from 1256 stroke patients were reviewed. In-hospital mortality was 5.3% in patients not on lipid-lowering agents and 1.0% in patients taking lipid-lowering therapy, a reduction of 82%. Furthermore, more pa&shy;tients on lipid-lowering therapy had mild events and fewer had severe events compared with those not on lipid-lowering therapy.

The need for detailed care programs once patients were discharged was also less among the patients on lipid-lowering agents, said Ms Allen.

• Statin withdrawal in the acute phase of stroke increases the risk of a poor neurologic outcome, said Floren&shy;tino Nombela, MD, a neurologist at University Hospital de la Princesa in Madrid.

“The statin withdrawal syndrome can play a negative role that must not be forgotten when managing patients in the acute phase of ischemic stroke,” he said.

His study included 215 patients with acute ischemic stroke, 89 of whom were taking statins at the time of their stroke. These 89 patients were randomized to either statin withdrawal during the first 3 days or continued drug therapy. A third group of 126 patients not on a statin at the time of their stroke served as controls. All patients received a statin after day 3.

Early neurologic deterioration, de&shy;fined as a decrease of 4 or more points on the National Institutes of Health Stroke Scale within the first 48 hours of hospital admission, occurred in 65.2% of patients who had statins withdrawn on admission compared with 20.9% who remained on statins. In the control group, early neurologic deterioration was experienced by 27%.

Scores of 2 or more points on the modified Rankin scale at 3 months were observed in 58.7% of patients who had their statin withdrawn, 37.2% of those who remained on a statin, and 42.1% of the controls.

Infarct volume at days 4 to 7 in&shy;creased by a mean of 74 cc in the group in whom statins were withdrawn compared with 26 cc in the group that remained on statins and 53 cc in the group that was not on a statin at admission.

Biomarkers offer complementary information on risk following stroke

Kissimmee, Fla—In a multiethnic population, the biomarker lipoprotein-associated phospholipase A2 (Lp-PLA2) is a strong predictor of stroke recurrence, whereas the acute phase reactant high-sensitivity C-reactive protein (hsCRP) is a strong predictor of mortality after stroke, said Mitchell S. Elkind, MD, at the American Stroke Association’s In&shy;ter&shy;national Stroke Con&shy;ference 2006.

The 2 markers together “appear to pro&shy;vide complementary information after a first ischemic stroke,” he said.

Lp-PLA2 is a macrophage-derived enzyme involved in metabolism of low-density lipoprotein to proinflammatory mediators. It was recently approved by the FDA for predicting the risk of a first ischemic stroke—it being the only biomarker approved for this purpose.

The Centers for Disease Control and Prevention and the American Heart Association had previously stated that the use of hs-CRP may help in predicting the risk of cardiovascular events in intermediate-risk patients.

In the Northern Manhattan Stroke Study, patients aged 40 years or older with a first ischemic stroke were followed for a median of 4 years to identify the utility of biomarkers for predicting recurrent stroke. Of the 467 patients who had levels of Lp-PLA2 and hsCRP measured, 55% were women, 53% were Hispanic, 27% were African American, and 18% were Caucasian. During the follow-up, 80 recurrent strokes were re&shy;corded. The levels of both biomarkers were categorized by quartile.

Slightly more than half of the participants had mild strokes as defined by the National Institutes of Health Stroke Scale, about one third had moderately severe strokes on this scale, and slightly less than 20% had severe strokes.

In unadjusted analyses, hsCRP was not associated with the risk of recurrent stroke, but patients whose levels of Lp-PLA2 were in the highest quartile had twice as many strokes as patients with Lp-PLA2 levels in the lowest quartile. An elevation in either marker also predicted an increased risk of death and a combined end point of stroke, myocardial infarction (MI), and death.

When adjusting for demographics, hypertension, diabetes, hyperlipidemia, smoking, atrial fibrillation, and coronary disease, hsCRP was no longer a significant predictor of recurrent stroke or the composite of stroke, MI, and death, but hsCRP levels in the highest quartile were still associated with a significant doubling of the risk of death compared with hs-CRP levels in the lowest quartile.

In contrast, Lp-PLA2 remained a significant predictor of recurrent stroke, with a doubling of risk with levels in the highest versus lowest quartile, and its predictive strength was attenuated but still significant for stroke, MI, and death, but it was no longer associated with the risk of death.

“Lp-PLA2 appears to provide information about the risk of recurrent stroke and other vascular events, and hsCRP provides information about mortality,” said Dr Elkind, assistant professor of neurology, Division of Stroke and Critical Care, Columbia University, New York City.

He added, “Because women and minorities are at higher risk for stroke and yet are relatively medically underserved, these findings may have special importance.”