Author + information
- Amy C. Alman, PhD∗ (, )
- John E. Hokanson, PhD,
- Gregory L. Kinney, PhD, MPH,
- David M. Maahs, MD, PhD,
- Marian J. Rewers, MD, PhD and
- Janet K. Snell-Bergeon, PhD, MPH
- ↵∗Department of Epidemiology and Biostatistics, College of Public Health, University of South Florida, 13201 Bruce B. Downs Boulevard, MDC 56, Tampa, Florida 33612.
The use of small Agatston scores to indicate the presence of coronary artery calcium (CAC) as a marker of atherosclerosis is controversial and may depend on the study population. Two studies found increased associations with all-cause mortality and incident cardiovascular events with low CAC (>0 to 10 AU) compared with none; however, the study populations were older (mean ages of 58 and 54 years, respectively) (1,2). In contrast, another study found no significant association between low CAC (>0 to 10 AU) and incident cardiovascular events in a younger population (mean age 43 years) (3). The significance of low CAC scores in younger populations is unclear. Therefore, we examined whether progression of CAC over 6 years was increased in participants with low CAC compared with individuals with zero CAC in the CACTI (Coronary Artery Calcification in Type 1 Diabetes) study. The CACTI study is a prospective cohort study of the prevalence and progression of CAC in a young population of adults with and without type 1 diabetes mellitus (T1DM).
Study participants were 19 to 56 years of age with T1DM (n = 442) or without diabetes (n = 506) who enrolled in the CACTI study in 2000 to 2002 and completed follow-up after 6 years. All participants reported no diagnosis of cardiovascular disease and were asymptomatic at enrollment. The protocol was reviewed and approved by the Colorado Multiple Institutional Review Board, and informed consent was obtained. The study has been described in detail elsewhere (4).
CAC was obtained using an ultrafast Imatron C-150XLP electron beam computed tomography scanner (Imatron, San Francisco, California). Progression was defined as an increase in volume of CAC between baseline and follow-up of ≥2.5 square root–transformed units (5).
Baseline CAC was categorized as 0, >0 to 10, >10 to 100, and >100 AU. Multivariate logistic regression was used to determine the association of baseline CAC on progression of CAC. All analyses were performed using SAS/STAT software version 9.3 (SAS Institute, Inc., Cary, North Carolina).
The study population was relatively young at baseline, with 48.8% of participants <40 years of age. Participants with T1DM were significantly younger than participants without diabetes (37 vs. 41 years; p < 0.001), had lower total cholesterol (172 vs. 194 mg/dl; p < 0.001), lower low-density lipoprotein cholesterol (98 mg/dl vs. 117 mg/dl; p < 0.001), higher systolic blood pressure (117 mm Hg vs. 115 mm Hg; p < 0.001), and a higher urine albumin creatinine ratio (71 μg/mg vs. 9 μg/mg; p < 0.001). At the baseline study visit, 64% of participants with T1DM and 72% of nondiabetic participants had zero CAC on both baseline scans. In both groups, 16% had low CAC at baseline (>0 to 10 AU).
From baseline to 6 years, CAC progressed in 42% of participants with T1DM compared with 30% of the nondiabetic participants (p < 0.001). Figure 1 displays the percent of participants with CAC progression according to diabetes status and baseline CAC category, with a significant trend across all CAC categories (p < 0.001).
In logistic regression analysis adjusted for age, sex, diabetes status, body mass index, glycosylated hemoglobin, and albumin creatinine ratio, a CAC score >0 to 10 AU was associated with a 2.5-fold increase in odds for progression (odds ratio: 2.5 [95% confidence interval: 1.6 to 3.9]). A mild CAC score (>10 to 100 AU) was associated with a 12-fold increase in odds for progression (odds ratio: 12.0 [95% confidence interval: 6.2 to 23.1]). The relationship between baseline CAC and progression did not differ by diabetes status.
We have shown, in a young population of individuals with T1DM and a similarly aged group of nondiabetic individuals, that the presence of CAC at low levels (>0 to 10 AU), is significantly associated with progression over 6 years of follow-up. Although the risk of the progression of CAC may be modest with low CAC scores, it is significantly higher than for zero CAC. These results are important for understanding the significance of low CAC on computed tomography scans and for determining clinically important values for use in future research.
Please note: Financial support was provided by the National Institutes of Health (National Heart, Lung, and Blood Institute grants R01 HLR01113029, R01 HL61753, and R01 HL079611). Dr. Snell-Bergeon was supported by the American Diabetes Association Jr. Faculty Award 1-10-JF-50. The CACTI study was also partially supported by the Clinical Translational Research Center at the University of Colorado Denver, which was supported by the National Institutes of Health M01 RR000051. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
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