Background: Low ankle-brachial index (ABI) is associated with increased risk of subsequent cardiovascular disease events, independent of Framingham risk factors, but its ability to improve risk prediction prospectively has not been examined.
Methods: We conducted post-hoc analysis of data from Atherosclerosis Risk in Communities Study (ARIC Study), a large prospective cohort study. 11,594 white and African American (24.2%) men and women, aged 45-64 years, with available Framingham Risk Score (FRS) variables and ABIs at baseline, and without known history of cardiovascular disease or diabetes mellitus or known peripheral arterial disease at baseline were assessed for hard cardiovascular events (hCVD; defined as heart attack, coronary death or stroke) over median follow-up of 10 years. Hazard ratios, C statistic, and net reclassification indexes were calculated to determine the independent predictive ability of ABI compared with FRS.
Results: 659 hCVD events occurred. Standardized ABI was significantly associated with hCVD events but with a relatively small effect on events (hazard ratios of 0.85 per standard deviation (95% CI 0.79-0.91) (p-value<0.0001)). The C statistic of FRS modified with ABI was only modestly improved (0.756-0.758). Net reclassification improvement, an indicator of prospective prediction performance, using an ABI threshold of 0.9 was small and statistically insignificant (0.8%, p=0.50).
Conclusions: Although the ABI adjusted for Framingham risk variables was independently associated with subsequent events in terms of hazard ratios, the independent effect of ABI when adjusted for FRS was small in magnitude, and the FRS performed similarly with or without integration or supplementation with ABI. These findings do not provide strong evidence to support FRS modification to include ABI.
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