Intensive glucose-lowering therapy reduces cardiovascular disease events in veterans affairs diabetes trial participants with lower calcified coronary atherosclerosis - PubMed (original) (raw)
. 2009 Nov;58(11):2642-8.
doi: 10.2337/db09-0618. Epub 2009 Aug 3.
Thomas E Moritz, Dawn C Schwenke, Robert J Anderson, Michael Criqui, Robert Detrano, Nicholas Emanuele, Moti Kayshap, Jennifer Marks, Sunder Mudaliar, R Harsha Rao, Jayendra H Shah, Steven Goldman, Domenic J Reda, Madeline McCarren, Carlos Abraira, William Duckworth; Veterans Affairs Diabetes Trial
Affiliations
- PMID: 19651816
- PMCID: PMC2768182
- DOI: 10.2337/db09-0618
Intensive glucose-lowering therapy reduces cardiovascular disease events in veterans affairs diabetes trial participants with lower calcified coronary atherosclerosis
Peter D Reaven et al. Diabetes. 2009 Nov.
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: At baseline, 301 type 2 diabetic participants in the VADT, a randomized trial comparing the effects of intensive versus 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 end points.
Results: During a median follow-up duration of 5.2 years, 89 cardiovascular events occurred. 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 (HRs) 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. Among those randomized to intensive treatment, for the subgroup with CAC >100, 11 of 62 individuals had events, while only 1 of 52 individuals with CAC < or = 100 had an event. The multivariable HR for intensive treatment for those with CAC >100 was 0.74 (95% CI 0.46-1.20; P = 0.21), while for the subgroup with CAC < or = 100, the corresponding HR was 0.08 (0.008-0.77; P = 0.03), with event rates of 39 and 4 per 1,000 person-years, respectively.
Conclusions: These data indicate that intensive glucose lowering reduces cardiovascular events in those with less extensive calcified coronary atherosclerosis.
Figures
FIG. 1.
Time course of A1C levels for intensive (INT) and standard (STD) treatment groups. Median levels of A1C are shown by study year (0 = baseline); the P value for the overall difference between groups is <0.01. Shown above the _x_-axis are the total number of participants at baseline and the beginning of each follow-up year through year 6.
FIG. 2.
Kaplan-Meier curves for time to primary macrovascular end point by clinical categories of CAC (0–10 [_A_], 11–100 [_B_], 101–400 [_C_], and >400[_D_]) in those randomized to the standard (Std) or intensive (Int) therapy arm. Differences between treatment groups were significant in A (P = 0.03). Shown above the _x_-axes are the total numbers of participants at risk at baseline and the beginning of each follow-up year through year 6.
FIG. 3.
HRs (95% CI) for effect of treatment (intensive vs. standard) in multivariable-adjusted models. Boxes represent HRs, and lines indicate 95% CI. P values indicate the significance of treatment effect in the indicated models. The treatment effect was estimated for high- and low-CAC subgroups separately (upper portion of figure) or for specific CAC scores (lower portion of figure) within a multivariable model including log(CAC + 1) as a continuous variable, treatment, and the calcium-treatment interaction effect. Multivariable models included age, ethnicity, diabetes duration, history of hypertension, history of smoking, prior CVD history, total and HDL cholesterol, and A1C as covariates.
Comment in
- Diabetes. 58:2448.
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References
- Khaw KT, Wareham N, Bingham S, Luben R, Welch A, Day N: Association of hemoglobin A1c with cardiovascular disease and mortality in adults: the European prospective investigation into cancer in Norfolk Ann Intern Med 2004; 141: 413– 420 - PubMed
- Selvin E, Marinopoulos S, Berkenblit G, Rami T, Brancati FL, Powe NR, Golden SH: Meta-analysis: glycosylated hemoglobin and cardiovascular disease in diabetes mellitus Ann Intern Med 2004; 141: 421– 431 - PubMed
- Laakso M: Hyperglycemia and cardiovascular disease in type 2 diabetes Diabetes 1999; 48: 937– 942 - PubMed
- UK Prospective Diabetes Study (UKPDS) Group UKPDS: intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33) Lancet 1998; 352: 837– 853 - PubMed
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