Intima-media thickness may improve cardiac risk prediction, study suggests

Adding a measurement of the maximum intima-media thickness of the internal carotid artery may increase the prognostic value of the Framingham risk score for cardiovascular events, according to a new study.

Researchers measured the mean intima-media thickness of the common carotid artery and the maximum intima-media thickness of the internal carotid artery in members of the Framingham Offspring Study cohort to examine whether these values would affect cardiac risk prediction when added to the Framingham risk score. Participants were followed for an average of 7.2 years for outcomes of cardiovascular disease, and cardiovascular risk was reclassified according to 8-year Framingham categories (i.e., low, intermediate or high) after intima-media thickness was added. The results of the study, which was funded by the National Heart, Lung, and Blood Institute, were published in the July 21 New England Journal of Medicine.

A total of 2,965 participants with no history of cardiovascular disease were included in the study. All were part of the Framingham Offspring Study's sixth examination cycle, which took place from February 1995 through September 1998. The mean age of participants was 58 years, all were white, and 1,629 (55.3%) were women. Two hundred ninety-six first cardiovascular events occurred during the follow-up period. For these events, the standard Framingham risk score had a C-statistic of 0.748 (95% CI, 0.719 to 0.776).

When intima-media thickness measurements were added to the Framingham risk factors, the adjusted hazard ratios for cardiovascular disease were 1.13 (95% CI, 1.02 to 1.24) per 1-SD increase in mean intima-media thickness of the common carotid artery and 1.21 (95% CI, 1.13 to 1.29) for maximum intima-media thickness of the internal carotid artery. The corresponding C-statistics increased by 0.003 (95% CI, 0.000 to 0.007) and 0.009 (95% CI, 0.003 to 0.016), respectively.

When study participants' risk was reclassified according to the new risk scores, intima-media thickness of the internal carotid artery was associated with a significant increase in the net reclassification index (7.6%, P<0.001), but intima-media thickness of the common carotid artery was not (0.0%; P=0.99). When the presence of plaque, or an internal carotid artery intima-media thickness greater than 1.5 mm, was added to the model, the net reclassification index was 7.3% (P=0.01), and the C-statistic increased by 0.014 (95% CI, 0.003 to 0.025).

The authors noted that their study involved only white participants and that the follow-up period, 7.2 years, was shorter than the 10-year period for which the Framingham risk score was developed, among other limitations. However, they concluded that intima-media thickness of both arteries predicted cardiovascular outcomes but that only measures of the internal carotid artery yielded significant improvement in cardiovascular risk classification.

“We believe the intima-media thickness of the internal carotid artery should be measured in addition to the thickness of the common carotid artery for purposes of cardiovascular risk assessment,” they wrote, cautioning that they measured this variable “offline” with an algorithm and their results might therefore be different from those obtained on ultrasonography. They called for further studies to determine how the presence of plaque affects cardiovascular risk stratification.