SAN DIEGO—Increasing evidence indicates that hypercholesterolemia, as well as increased low-density lipoprotein (LDL) cholesterol levels and decreased high-density lipoprotein (HDL) cholesterol levels, may be a risk factor for carotid atheroma and ischemic stroke, according to Ralph L. Sacco, MD. Mounting data also suggest that taking statins, especially by patients in certain high-risk categories, may help reduce that risk.

"I do believe, and I think the data suggest, that cholesterol is a stroke risk factor," said Dr. Sacco, at the 58th Annual Meeting of the American Academy of Neurology. "It may not be the strongest, but it is prevalent and may be important when we think about the number of strokes attributed to elevated cholesterol. It may be differential by stroke subtype. Statins clearly reduce stroke risk among high-risk patients—for example, those with coronary artery disease, diabetes, and hypertension—and have a role in secondary stroke prevention." Dr. Sacco is a Professor of Neurology and Epidemiology at the Neurological Institute of Columbia University College of Physicians and Surgeons in New York City and Chair of the Stroke Advisory Committee of the American Stroke Association.

Advances in primary and secondary stroke prevention could have a significant impact in the overall treatment of stroke, according to Dr. Sacco. The prevalence of hypercholesterolemia makes it a prime target in that effort, as about 43% of men and 36% of women in the United States have an elevated LDL cholesterol level, defined as greater than 130, noted Dr. Sacco. "So even if it is a mild risk factor, its prevalence implies that it would have a big effect in terms of number of strokes attributed to this risk factor," he said.

STROKE AND CHOLESTEROL

In addition, whereas older trials did not involve statins, more recent randomized clinical trials with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors have shown that effective lowering of cholesterol levels substantially reduces the risk of cardiac disease and stroke, said Dr. Sacco. "The good news is that there are multiple studies regarding statins that are randomized, and therefore the evidence is great," he said.

The latest endorsement for the use of statins in stroke prevention was provided by the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial, results of which were reported at the 15th European Stroke Conference. Investigators found that atorvastatin, 80 mg/day, significantly reduced the risk of recurrent stroke in patients without coronary heart disease who had normal cholesterol levels. The 10-year international study included more than 4,700 patients with a stroke or transient ischemic attack within the previous six months. The atorvastatin regimen reduced stroke risk by 16%, major coronary events by 35%, coronary heart disease events by 42%, and revascularization procedures by 45%.

WHO BENEFITS?

Other statin trials involving medium- to lower-risk patients have not been as clear in terms of stroke outcome. The Prospective Study of Pravastatin in the Elderly at Risk trial found a reduced risk of coronary artery disease, though stroke risk was unaffected. "The effect of statins for primary stroke prevention may be less than that, say, for higher-risk individuals," said Dr. Sacco.

MULTIPLE BENEFITS OF STATINS

In addition to aiding cholesterol reduction, statins may also lead to improved endothelial function, reduced inflammation, stabilization and reduction in atherosclerotic plaques, and attenuated thrombogenic responses, suggested Dr. Sacco. "Some of these cholesterol-independent effects are important and have brought us more basic science evidence to go from the bedside back to the bench and maybe even back to the bedside with some translational work," he said.

Retrospective data have also revealed favorable outcomes among those who took statins at the time of a stroke. Elkind et al, in the Northern Manhattan Study, observed a lower 90-day mortality among patients taking statins at the time of stroke. Parra and colleagues found that in patients with acute aneurysmal subarachnoid hemorrhage, those who used statins demonstrated significant improvement in 14-day functional outcomes. "So there is beginning evidence in humans, retrospectively albeit for now, that suggests that statins may have an effect that would go beyond what we would expect by just LDL lowering," said Dr. Sacco.

"I think in the future, based on the results of this translational work, statins could have a role as an acute stroke therapy," Dr. Sacco continued. "The availability of more effective preventive treatments for stroke will greatly improve our ability to modify the risk of ischemic stroke and substantially reduce the number of persons killed or disabled by stroke each year."

NR