High Cholesterol Elevates Women's Risk Of Stroke Death

"Most prior research has had too few women, especially minority women, to firmly establish the relationship between cholesterol and stroke mortality," says Lori Mosca, M.D., Ph.D., senior author and associate professor of medicine at Columbia University College of Physicians & Surgeons in New York.

The results also confirmed the importance of the traditional risk factors for stroke death including high blood pressure and diabetes. Early studies of risk factors for stroke death showed inconsistent associations between cholesterol and stroke death. Recently, studies in patients with known cardiovascular disease have shown that treatment with cholesterol-lowering drugs reduced the risk of stroke death. Reflecting the recent findings, the American Heart Association last year cited cholesterol as a stroke risk factor in a scientific statement on stroke prevention.

Researchers followed participants in eight large, long-term prospective studies that formed The Women's Pooling Project (WPP). They evaluated stroke risk factors in 24,343 women with no history of heart attack, coronary chest pain, or stroke. They were 30-97-years old (average 52) at the time of enrollment, with 17.4 percent African-Americans, and 4.9 percent Hispanic. The women were followed for a total of 339,215 patient-years (the number of women times the number of years they were each followed). Some patients were followed for 20 years or longer.

A total of 568 stroke-related deaths occurred during follow-up, representing about 10 percent of all deaths. Consistent with other stroke studies, researchers found that more than 80 percent of the stroke deaths (461) were associated with strokes caused by clots or narrowing of vessels that carry blood to the brain. Most of the remaining deaths involved strokes caused by bleeding in the brain.

For the entire study population, cholesterol levels averaged about 225 milligrams per deciliter (mg/dL). Researchers divided the population into five groups according to total cholesterol levels. Average total cholesterol levels for the five groups ranged from a low of about 162 mg/dL to a high of 290 mg/dL. The entire population also was analyzed by age, grouping 14,305 women who were younger than 55 at enrollment and 10,038 who were 55 and older. The average age of the under 55 group was 44.3-years-old and the average age of the 55 and older group was 62.7-years-old.

Cholesterol proved to be a significant risk factor for stroke death in women younger than 55 at enrollment. The risk for ischemic (clot-related) stroke death increased by 23 percent across the entire spectrum of cholesterol levels, revealing a continuous association between rising cholesterol levels and increased stroke death risk. For women younger than age 55 at enrollment, the average age of stroke death was 63.

Cholesterol did not predict hemorrhagic (bleeding) stroke mortality in younger women. Additionally, cholesterol did not have a significant association with stroke death in older women.

The analysis also showed that African-American women faced a significantly greater risk for stroke death compared to white women. The risk for African-American women was 76 percent greater in the younger age group and 48 percent greater in the older age group. The risk was more than double among younger African-American women with the highest cholesterol levels compared to those with the lowest cholesterol levels. The difference persisted after accounting for other factors including blood pressure, diabetes, smoking, and obesity.

High cholesterol contributes to stroke risk through several mechanisms – including its role in the development of coronary heart disease, a subsequent increase in atrial fibrillation and left ventricular dysfunction. Atrial fibrillation (AF) is a disorder in which the two small, upper chambers of the heart quiver instead of beating effectively. Blood in these chambers may form clots. If a clot leaves the heart and lodges in an artery to the brain, a stroke results. In addition, high cholesterol also contributes to plaque buildup in the blood vessels leading to the brain, as well as in the vessels of the brain itself. A blockage in these vessels causes an ischemic stroke.

This study also affirms the value of stroke prevention efforts aimed at other controllable risk factors, such as high blood pressure, diabetes and smoking, adds Mosca, who is also director of preventive cardiology at New York-Presbyterian Hospital. Moreover, the results emphasize that prevention should include consideration of the long-term consequences of elevated cholesterol levels in relatively young women.

Rose Marie Robertson, M.D., professor of medicine at Vanderbilt University and a past president of the American Heart Association, commented on the study:

"I hope that these findings will help us convince young women and their physicians that an aggressive approach to identifying and controlling risk factors at an early age – certainly long before women begin to be concerned about stroke – is not only worthwhile, it is essential."

Co-authors are Richard B. Horenstein, M.D. and Dean E. Smith, Ph.D. The study was funded in part by the American Heart Association and the National Heart, Lung, and Blood Institute.