DALLAS, May 23 - A gene mutation that raises levels of triglycerides, a major type of fat in the body, doubles the risk of developing blockages in the brain that can lead to a stroke, researchers report in today's Circulation: Journal of the American Heart Association.
Like elevated cholesterol, high triglycerides are associated with atherosclerosis -- a build up of vessel-narrowing fatty deposits in arteries feeding the heart and brain.
"It is a significant finding that about 5 percent of Danish women, and probably 5 percent of all white women carry a mutation that may increase trigylceride concentration in their blood. This increase may double their risk of both heart disease and stroke," says Hans H. Wittrup, M.D., Ph.D., the lead author of the report.
The new study follows up on an earlier one by the Danish team which indicated that a defect in the gene for an enzyme called lipoprotein lipase -- an enzyme that breaks down triglycerides -- doubled the risk of heart disease in women, but not in men.
The same process that clogs heart arteries can narrow the carotid arteries carrying blood to the brain. "Approximately 20 percent of individuals who experience a stroke also have moderate to severe amounts of atherosclerosis in their brain blood vessels, or carotids," says Wittrup, a fellow at Herlev University Hospital, Denmark. "Thus, it was a logical step to follow up the findings on increased risk of heart disease and to investigate the increased risk of stroke."
If further research confirms that the mutation is a risk factor, it will help physicians better identify certain women with this defect who are at greater risk for developing heart disease and stroke. However, Wittrup emphasizes that such controllable factors as high blood pressure elevated cholesterol, and smoking pose much greater stroke risks for women, as well as men, than the gene mutation.
Prior to the Danish studies, other researchers had shown that when a person inherited a mutated lipoprotein lipase gene from each parent -- a roughly 1 in 1 million event -- the result was a 5- to 15-fold increase in blood triglycerides. The work by Wittrup and his colleagues showed that inheriting a single defective gene also increased the risk of elevated triglycerides in women.
The Danish researchers examined a mutation designated 291 because it causes a lower production of the enzyme and is found among people in several parts of the world.
In their new study, the team looked at two separate groups of individuals who had suffered nonfatal strokes and compared each to a control group. Members of both control groups were chosen from the general Danish population and had not suffered a stroke.
Overall, the study found that risk of stroke was not linked to the presence of the gene. However, women with the mutated gene had a risk of having blockages of roughly twice that of women who didn't have the mutation. The men with the mutated gene did not have an increased risk of reblockages.
The researchers do not know why women with the mutation have a greater risk of elevated triglycerides and risk of stroke than men. However, Wittrup and his colleagues offer several possible suggestions.
"Triglyceride concentrations in blood are a better predictor of atherosclerosis in women than in men," Wittrup says. "Therefore, a mutation that elevates triglyceride concentration in the blood may also have a greater effect on risk of heart disease and stroke in women than in men."
Two other possibilities are that the female hormone estrogen may decrease the concentration of lipoprotein lipase in the blood. A decreased level would lead to an increase in triglycerides. Furthermore, the male sex hormone testosterone may decrease the effect of the 291 mutation in men but not women.
CONTACT:
For journal copies only,
please call: (214) 706-1173
For other information, call:
Carole Bullock: (214) 706-1279 caroleb@heart.org
Brian Henry: (214) 706-1135
Co-authors are Børge G. Nordestgaard, M.D., D.M.Sc.; Henrik Sillesen, M.D., D.M.Sc.; Peter Schnohr, M.D.; and Anne Tyjae-Hansen, M.D., D.M.SC.
Dr. Wittrup can be reached by telephone at 011-45-70-202-202, or by fax at 011-45-26250099 or by e-mail at HANS@wittrup.net. Dr. Tybjaerg-Hansen can be reached by telephone at 011-45-35454159, or by fax at 011-45-354522524 or by email at AT-H@RH.DK, and Dr Nordestgaard by telephone at 011-45-44883311 or by e-mail BRNO@HERLEVHOSP.XBHAMT.DK (Please do not publish these numbers.)