Carotid-wall intima-media thickness and cardiovascular events

Abstract

Background: Intima-media thickness of the walls of the common carotid artery and internal carotid artery may add to the Framingham risk score for predicting cardiovascular events.

Methods: We measured the mean intima-media thickness of the common carotid artery and the maximum intima-media thickness of the internal carotid artery in 2965 members of the Framingham Offspring Study cohort. Cardiovascular-disease outcomes were evaluated for an average follow-up of 7.2 years. Multivariable Cox proportional-hazards models were generated for intima-media thickness and risk factors. We evaluated the reclassification of cardiovascular disease on the basis of the 8-year Framingham risk score category (low, intermediate, or high) after adding intima-media thickness values.

Results: A total of 296 participants had a cardiovascular event. The risk factors of the Framingham risk score predicted these events, with a C statistic of 0.748 (95% confidence interval [CI], 0.719 to 0.776). The adjusted hazard ratio for cardiovascular disease with a 1-SD increase in the mean intima-media thickness of the common carotid artery was 1.13 (95% CI, 1.02 to 1.24), with a nonsignificant change in the C statistic of 0.003 (95% CI, 0.000 to 0.007); the corresponding hazard ratio for the maximum intima-media thickness of the internal carotid artery was 1.21 (95% CI, 1.13 to 1.29), with a modest increase in the C statistic of 0.009 (95% CI, 0.003 to 0.016). The net reclassification index increased significantly after addition of intima-media thickness of the internal carotid artery (7.6%, P<0.001) but not intima-media thickness of the common carotid artery (0.0%, P=0.99). With the presence of plaque, defined as intima-media thickness of the internal carotid artery of more than 1.5 mm, the net reclassification index was 7.3% (P=0.01), with an increase in the C statistic of 0.014 (95% CI, 0.003 to 0.025).

Conclusions: The maximum internal and mean common carotid-artery intima-media thicknesses both predict cardiovascular outcomes, but only the maximum intima-media thickness of (and presence of plaque in) the internal carotid artery significantly (albeit modestly) improves the classification of risk of cardiovascular disease in the Framingham Offspring Study cohort. (Funded by the National Heart, Lung, and Blood Institute.).

Figure 1. Kaplan–Meier Estimates of the Probability of New-Onset Cardiovascular Disease (CVD)

Data are shown for all 2946 participants overall (Panel A) and according to the category of Framingham risk score for CVD: low risk (0 to <6%) (Panel B), intermediate risk (6 to 20%) (Panel C), and high risk (>20%) (Panel D). In the low-risk category, 134 of the 1191 persons had plaque, for a prevalence of 11.3%, and the 8-year rates of cardiovascular disease were 2.5% and 11.0% among persons without plaque and those with plaque, respectively (P<0.001) (Panel B). In the intermediate-risk category, 513 of the 1382 persons had plaque, for a prevalence of 37.1%, and the 8-year rates of cardiovascular disease were 8.5% and 15.1% among persons without plaque and those with plaque, respectively (P<0.001) (Panel C). In the high-risk category, 257 of the 373 persons had plaque, for a prevalence of 68.9%, and the 8-year rates of cardiovascular disease were 17.0% and 36.7% among persons without plaque and those with plaque, respectively (P = 0.004) (Panel D).