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 recent studies found increased associations with all-cause mortality and incident cardiovascular events with low CAC (>0–10 AU) compared to none, however, the study populations were older (mean ages of 58 and 54, respectively) (1,2). In contrast, another recent study did not find any significant association between low CAC (>0–10 AU) and incident cardiovascular events in a younger population (mean age 43) (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 when compared to individuals with zero CAC in the Coronary Artery Calcification in Type 1 Diabetes (CACTI) 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 (T1D).
Study participants were 19–56 years of age with T1D (N=442) or without diabetes (N=506) who enrolled in the CACTI study in 2000–2002 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, CA). 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, >0–10, >10–100, 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].
The study population was relatively young at baseline, with 48.8% of participants under the age of 40. Participants with T1D were significantly younger than participants without diabetes (37 years vs. 41 years, p<0.001), had lower total cholesterol (172 mg/dl vs. 194 mg/dl, p<0.001), lower LDL-cholesterol (98 mg/dl vs. 117 mg/dl, p<0.001), higher systolic blood pressure (117 mmHg vs. 115 mmHg, p<0.001), and higher urine albumin creatinine ratio (ACR) (71 µg/mg vs. 9 µg/mg, p<0.001). At the baseline study visit, 64% of participants with T1D and 72% of non-diabetic participants had zero CAC on both baseline scans. In both groups, 16% had low CAC at baseline (>0–10 AU).
From baseline to 6 years CAC progressed in 42% of participants with T1D vs. 30% of non-diabetic participants (p<0.001). Figure 1 shows the percentage of participants with CAC progression by diabetes status and baseline CAC category, with a significant trend across all CAC categories (p<0.001).
Figure 1. Progression of CAC by baseline CAC categories.
Percentage of participants with progression of CAC at year 6 by baseline CAC category and diabetes status, showing more than twice as many study participants with a low CAC score >0–10 having CAC progression than participants with zero CAC (test for trend p<0.001).
In logistic regression analysis adjusted for age, sex, diabetes status, BMI, HbA1c, and ACR, a CAC score of >0–10 was associated with a 2.5-fold increased odds for progression (OR 2.5, 95% CI 1.6–3.9). A mild CAC score (>10–100) was associated with a 12-fold increased odds for progression (OR 12.0, 95% CI 6.2–23.1). The relationship between baseline CAC and progression did not differ by diabetes status.
We have shown, in a young population of individuals with T1D and similar age non-diabetic individuals, that the presence of CAC at low levels (>0–10), is significantly associated with progression over 6 years of follow-up. While 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 CT scans and for determining clinically important values for use in future research.
Acknowledgments
Financial support was provided by the NIH 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 CTRC at the University of Colorado Denver supported by the NIH M01 RR000051.
Footnotes
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Disclosures:
There are no relationships to industry to report.
The authors report no conflict of interest.
REFERENCES
- 1.Budoff MJ, McClelland RL, Nasir K, et al. Cardiovascular events with absent or minimal coronary calcification: the Multi-Ethnic Study of Atherosclerosis (MESA) Am Heart J. 2009;158:554–561. doi: 10.1016/j.ahj.2009.08.007. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Blaha M, Budoff MJ, Shaw LJ, et al. Absence of coronary artery calcification and all-cause mortality. JACC Cardiovasc Imaging. 2009;2:692–700. doi: 10.1016/j.jcmg.2009.03.009. [DOI] [PubMed] [Google Scholar]
- 3.Taylor AJ, Fiorilli PN, Wu H, et al. Relation between the Framingham Risk Score, coronary calcium, and incident coronary heart disease among low-risk men. Am J Cardiol. 2010;106:47–50. doi: 10.1016/j.amjcard.2010.02.009. [DOI] [PubMed] [Google Scholar]
- 4.Dabelea D, Kinney G, Snell-Bergeon JK, et al. Effect of type 1 diabetes on the gender difference in coronary artery calcification: a role for insulin resistance? The Coronary Artery Calcification in Type 1 Diabetes (CACTI) Study. Diabetes. 2003;52:2833–2839. doi: 10.2337/diabetes.52.11.2833. [DOI] [PubMed] [Google Scholar]
- 5.Hokanson JE, MacKenzie T, Kinney G, et al. Evaluating changes in coronary artery calcium: an analytic method that accounts for interscan variability. AJR Am J Roentgenol. 2004;182:1327–1332. doi: 10.2214/ajr.182.5.1821327. [DOI] [PubMed] [Google Scholar]