Impaired endothelial function is an early indicator of atherosclerosis

Impaired endothelial function is an early indicator of atherosclerosis according to a study of healthy people followed from childhood to young adulthood reported in Circulation: Journal of the American Heart Association.

The Cardiovascular Risk in Young Finns Study is an ongoing five-center study of atherosclerosis precursors in Finnish children and adolescents begun in 1980.

At the 21-year follow-up in 2001, when the participants were young adults, researchers measured risk factors and other markers of atherosclerosis, including how well the inner layer of blood vessels functioned, which is called endothelial function.

“Our results emphasize the importance of endothelial health to prevent cardiovascular diseases. The data indicate that in addition to evaluating conventional cardiovascular risk factors, the noninvasive evaluation of endothelial dysfunction might be helpful to assess risk for atherosclerosis,” said study author Olli T. Raitakari, M.D., Ph.D., assistant professor of clinical physiology at the University of Turku in Finland.

Endothelial dysfunction impairs the blood vessels’ ability to dilate. Normally, the brachial artery (in the arm) dilates in response to increased blood flow (induced by such things as a blood pressure cuff squeezing and releasing the forearm). This dilation is directly related to the ability of arterial endothelial cells to produce and release nitric oxide.

Thus, impaired dilation reflects reduced production of nitric oxide, which can be regarded as an important marker of endothelial cell dysfunction.

Researchers measured endothelial function using flow-mediated dilatation (FMD) and used ultrasound to assess carotid intima-thickness (IMT) in 2,109 healthy adults aged 24 to 39 years. Carotid IMT is a measure of the thickness of the neck arteries that supply blood to the brain. It indicates the thickness of the artery wall, and is an accepted, noninvasive way to assess plaque buildup in the arteries.

“We believe that atherosclerosis is a diffuse disease that affects arteries universally,” Raitakari said. “Therefore, by measuring arterial wall thickness in carotid arteries, it is possible to get a general idea of the atherosclerotic involvement in the whole arterial tree.”

Higher IMT was associated with lower FMD, even after taking into account age, sex, brachial vessel size and several other variables.

The researchers classified subjects according to their FMD values as enhanced (average 16 percent dilation), intermediate (between 5 and 10 percent dilation) or impaired (average 1 percent dilation). The researchers found that the number of traditional cardiovascular disease risk factors was associated with increased IMT in people with impaired endothelial function, but not in people with enhanced FMD response.

A greater number of risk factors identified in childhood was associated with increased carotid IMT measured 21 years later (in adulthood) for people with impaired FMD but not in people with enhanced FMD.

“We had previously shown that risk factors in childhood predict atherosclerosis in adults, but we wanted to gain insight into the role of endothelial status in the early stages of atherosclerosis. The data suggest that enhanced vascular endothelium function in adulthood may protect the arteries against atherosclerosis in response to early life exposure to risk factors,” Raitakari said.

Studies are still needed to test whether endothelial dysfunction is an independent risk factor for the development of atherosclerosis and cardiovascular events, he added.

Co-authors are Markus Juonala, M.D.; Jorma S.A. Viikari, M.S., Ph.D.; Tomi Laitinen, M.D., Ph.D.; Jukka Marniemi, Ph.D.; Hans Helenius, M.Sc.; and Tapani Rönnemaa, M.D., Ph.D.

Statements and conclusions of study authors that are published in the American Heart Association scientific journals are solely those of the study authors and do not necessarily reflect association policy or position. The American Heart Association makes no representation or warranty as to their accuracy or reliability.