'Sticky' Blood May Underlie Development Of Early Atherosclerosis In Men

The increased risk does not hold true for women -- which may shed light on why males tend to develop heart disease and suffer strokes at a younger age than females, says lead author Amanda J. Lee, Ph.D., research statistician at the University of Edinburgh Medical School, Scotland.

The study is the first to link blood stickiness to the early development of atherosclerosis, which results from the build-up of cholesterol, fats and biological debris in the tissue lining the inside of blood vessels. This build-up can obstruct blood flow to the heart and brain and thereby cause a heart attack or stroke.

The researchers cannot explain the lack of correlation between blood viscosity and blood vessel-wall thickening in women. They do, however, have several hypotheses.

A number of risk factors contribute to the development of atherosclerosis, and an interaction may be required among these risk factors to cause the blood vessel damage that occurs in men. One interaction may involve cigarette smoking, which is greater in men than women. A more likely explanation, however, is that blood viscosity has a different effect in men than women, which accounts for its role in early blood vessel damage, Lee says.

Blood viscosity may act differently in the two sexes because of differences in speed of the blood as it courses through vessels and subtle differences between the two sexes in the geometry, or shape, of blood vessels, she says. A higher blood velocity in men, coupled with greater viscosity, cigarette smoking and blood pressure, may create greater sheer stress that does more damage in men than in women to the one-cell-thick inner lining of blood vessel walls.

This may preferentially predispose men to the buildup of deposits in the blood vessel walls that can eventually lead to heart attacks and strokes, Lee suggests. "Therefore, it may be that viscosity may explain why men have higher heart attack and strokes rates than women."

Previous studies identified blood viscosity and elevated levels of certain blood substances, including the protein fibrinogen, as increasing the risk of a heart attack or stroke caused by atherosclerotic disease. Other studies have shown that an increased thickness of the intima and the media, the two layers within the blood vessel wall where deposits form, can indicate early atherosclerosis.

"But nobody before us looked at the stickiness of blood and its various determinants to see whether they may have an effect on intima-media," she says.

Moreover, when the researchers statistically adjusted their findings to account for the role of cholesterol, age, blood pressure and cigarette smoking in blood vessel thickening, they found that sticky blood still increased the intima-media thickening risk in males.

"We've shown that these effects are independent of the known common risk factors, and so basically, we can say that viscosity has an effect on early atherosclerosis in men," Lee says.

She and her colleagues used data from the Edinburgh Artery Study, a prospective study of 1,592 men and women 55 to 74 years old when they were enrolled in the late 1980s. At the time of entry, each answered a risk-assessment questionnaire and gave blood. Five years later, as part of their follow-up, the volunteers were given a B-mode ultrasound scan, which can provide a image of the thickness of the intima and media layers in the blood vessels to the brain.

This ultrasound technique yields a black-and-white longitudinal image of a vessel from which thickness measurements can be made. "We're talking very small thicknesses-millimeters or parts of millimeters thick," Lee says. (One millimeter equals 0.0394 inch.).

The researchers compared the intima-media thickness measurements of 1,106 study participants with their blood-flow status and the levels of various substances in their blood. These included blood and plasma viscosity; packed red cell volume (hematocrit); fibrinogen, a protein involved in clotting; von Willebrand factor, which can indicate damage to cells lining the vessel; tissue plasminogen activator, an anticlotting factor; and fibrin D-dimer, an indicator of fibrinogen activity.

The study noted significant correlations in men -- but not in women -- between intima-media thickness and elevated blood viscosity and three major elements that determine blood stickiness: plasma viscosity, fibrinogen, and the red-blood-cell count.

Co-authors of the paper are Philip I. Mowbray, B.Sc.; Gordon D.O. Lowe, F.R.C.P.; Ann Rumley, Ph.D.; F. Gerald R. Fowkes, F.R.C.P.E.; and Paul L. Allan, F.R.C.R. The study was funded by the British Heart Foundation.