Abstract

Objective. This study investigated the hypothesis that baseline calcified coronary atherosclerosis may determine cardiovascular disease events in response to intensive glycemic control within the Veterans Affairs Diabetes Trial (VADT).

Research Design and Methods. 301 type 2 diabetes participants in the VADT, a randomized trial comparing the effects of intensive vs. standard glucose lowering on cardiovascular events, had baseline coronary atherosclerosis assessed by coronary artery calcium (CAC) measured by computed tomography. Participants were followed over the 7.5-year study for development of cardiovascular endpoints.

Results. 89 cardiovascular events occurred during a median follow-up duration of 5.2 years. Although intensive glucose lowering therapy did not significantly reduce cardiovascular events in the substudy cohort as a whole, there was evidence that the response was modified by baseline CAC as indicated by significant p-values for treatment by log (CAC+1) interaction terms in unadjusted and multivariable adjusted models (0.01 and 0.03, respectively). Multivariable adjusted hazard ratios (HR) for the effect of treatment indicated a progressive diminution of benefit with increasing CAC. Subgroup analyses were also conducted for clinically relevant CAC categories, those above and below an Agatston score of 100. For the subgroup with CAC > 100, 11 of 62 individuals had events, while only 1 of 52 individuals with CAC ≤100 suffered an event. The multivariable HR for intensive treatment for those with CAC > 100 was 0.74 (0.46-1.20, p=0.21), while for the subgroup with CAC ≤ 100, the corresponding HR was 0.08 (0.008-0.77, p=0.03), with event rates of 39 and 4 per 1000 person-years, respectively.

Conclusions. These data indicate that intensive glucose lowering reduces cardiovascular events in those with less extensive calcified coronary atherosclerosis.