A longitudinal study that followed healthy Finnish people from childhood to young adulthood adds evidence that impaired endothelial function is an early indicator of atherosclerosis, according to an article in the October 26th issue of Circulation.

The Cardiovascular Risk in Young Finns Study is an ongoing five-center study of atherosclerosis precursors in Finnish children and adolescents that began 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 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, MD, PhD.

Impaired dilation of the brachial artery in response to increased blood flow (such as that induced under testing situations by tightening and loosening of a blood pressure cuff) indicates decreased ability of the arterial endothelial cells to produce and release nitric oxide. This functional endothelial change has come to be regarded as an important marker of endothelial cell function.

In the current study, researchers measured endothelial function using flow-mediated dilatation and used ultrasound to assess carotid intima-thickness in 2,109 healthy adults age 24 to 39 years. Carotid intima-thickness directly 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.”

As would be expected, greater wall thickness was associated with lower flow-mediated dilatation scores, even after taking into account age, sex, brachial vessel size, and several other variables.

The researchers classified subjects according to their dilatation 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 intimal-wall thickness in people with impaired endothelial function, but not in people with enhanced flow-mediated dilatation response.

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

“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.