Coronary artery calcium in diabetic individuals

From the Department of Medicine, Section of Cardiology, University of Illinois College of Medicine; Department of Medical Surgical Nursing, University of Illinois College of Nursing; Division of Pediatric Endocrinology, University of Chicago; and Department of Preventive Medicine, Northwestern University School of Medicine, Chicago, Illinois

Cardiovascular disease is the major cause of death in people with diabetes and is responsible for two thirds of the deaths in this population.1-3 Because traditional coronary artery disease (CAD) risk factors account for only a

portion of the increased CAD risk in diabetes, researchers have been seeking a more accurate risk stratification tool.4 Electron-beam computed tomography (EBT) permits quantitative measurement of coronary artery calcium (CAC), a marker for atherosclerosis.5 An objective and individualized measure of the calcium component of the atherosclerotic plaque, such as EBT-CAC, may aid in the assessment of risk for future cardiovascular events. The

present study examines the age and sex distribution of CAC in a large co-hort of asymptomatic diabetic individuals compared with healthy control subjects.

Patients and methods

EBT-CAC screening was performed on 30,904 self-referred individuals without known CAD, ranging in age from 30 to 90 years. All subjects completed a questionnaire eliciting a history of smoking, diabetes, hypercholesterolemia, hypertension, and CAD in the family. The CAC score was determined according to the Agatston method.6 Details of the University of Illinois at Chicago scanning protocol have been published previously.7

Results

Diabetes was reported by 3.4% (747 of 22,188) of men and 3.8% (328 of 8,716) of women. Patients with diabetes were generally older and had a greater prevalence of hypertension, cigarette use, and CAC compared with subjects without diabetes. The mean (± SD) total CAC score in the diabetic group was 284 (± 684) compared with 106 (± 328) in subjects without diabetes. The prevalence figures for CAD risk factors in the present study were similar to those reported in the National Health and Nutrition Examination Survey (NHANES) and the Atherosclerosis Risk in Communities (ARIC) study.8,9 Pairwise comparisons of median CAC scores by sex, 5-year age groups, and diabetes status are shown in table 1. In all but three age groups, men and women with diabetes had higher median CAC scores. CAC scores did not differ between diabetic and nondiabetic individuals in three groups: women 40 to 44 years of age and both men and women aged 70 years and older. Within each 5-year age group, men with diabetes had consistently higher CAC scores than women with diabetes (P < .001 for all comparisons), except for the youngest age group (patients younger than 40 years; P = .05).

The age and sex CAC score percentile permits the ranking of an individual’s test result against a matched population.7 We examined the association between traditional CAD risk factors, including diabetes, and a total CAC score in the highest age and sex quartile. Logistic regression analysis showed a significant association between the variables for both men and women, with diabetes being the strongest predictor (table 2). Overall, the likelihood of having a CAC score in the highest age and sex quartile was 70% greater for diabetic individuals than for their nondiabetic counterparts. Because diabetic individuals were older than nondiabetic control subjects, their higher CAC scores could be attributable to older age and not diabetes status. To test this hypothesis, we matched a sample of 3,225 randomly selected nondiabetic control subjects by age and sex. Analysis by logistic regression showed that the associations between CAD risk factors and a total CAC score in the 75th age and sex percentile were similar to those reported for the unmatched sample. It was concluded, therefore, that diabetes was independently associated with a CAC score in the highest quartile for age and sex.

Discussion

The results of this observational study showed that, across most ages, asymptomatic diabetic men and women had higher median CAC scores than their nondiabetic counterparts. At any given age, diabetic men exhibited significantly greater calcified plaque burden than diabetic women. Diabetes was the strongest correlate for a CAC score in the highest age and sex quartile in both sexes among the CAD risk factors examined, even when using an age- and sex-matched sample of nondiabetic control subjects.

We examined the distribution of CAC in the largest sample of dia-

betic individuals reported to date. Other groups of researchers previously assessed the prevalence and extent of CAC in diabetes. In a recent study, Schurgin and colleagues evaluated the degree of CAC in a sample of 139 asymptomatic diabetic in-dividuals compared with a randomly selected nondiabetic group.10 Twenty-six percent of diabetic individuals had CAC scores ≥ 400, compared with a 7.2% prevalence of CAC in the nondiabetic group. Olson and colleagues found that CAC had 84% sensitivity for clinical CAD in men with type 1 diabetes and 71% sensitivity in women with type 1 diabetes.11 Khaleeli and colleagues reported a higher prevalence of CAC in 168 symptomatic (anginal) diabetic individuals compared with 155 asymptomatic individuals without diabetes.12 The authors did not find a significant difference between diabetic men and women with regard to CAC scores at any given age. The failure to show a significant difference, however, could be attributable to

the small sample size (n = 323) and the small correlation coefficients reported (r = 0.28 for men and r = 0.36 for women).

A few limitations to the present study should be considered. The reliance on self-reported rather than clinically measured CAD risk factors could be a limitation. In a peripheral study, however, high levels of agreement between self-reported and clinically measured diabetes status were found.13 Another possible limitation is that all study subjects were self-referred. Self-referred individuals may represent extremes of the population relative to health status. However, prevalence figures for CAD risk factors in our study sample were comparable with those reported in two large population-based studies.8,9

Whether EBT-CAC screening of asymptomatic diabetic individuals adds important information to traditional CAD risk factors remains unclear. In fact, diabetic individuals without known CAD are traditionally considered in the same risk category as nondiabetic individuals with known CAD.1 Thus, noninvasive testing such as EBT may do little to change the current clinical management of traditional CAD risk factors. Future studies examining the prognostic value of CAC in asymptomatic diabetic individuals will help delineate a role for EBT in the clinical management of diabetes.14

An important role for EBT-CAC screening in both diabetes and impaired glucose tolerance could be in tracking the natural history of coronary atherosclerosis as well as the changes induced by medical interventions. CAC screening may be particularly useful for identifying individuals who might require more aggressive management of risk factors among prediabetic individuals, especially those with the metabolic syndrome. Further research is needed to address these potential uses of CAC screening for individuals with diabetes and for those who are at risk for developing diabetes.