Elsevier

Atherosclerosis

Volume 209, Issue 2, April 2010, Pages 455-462
Atherosclerosis

Comparing coronary artery calcium and thoracic aorta calcium for prediction of all-cause mortality and cardiovascular events on low-dose non-gated computed tomography in a high-risk population of heavy smokers

https://doi.org/10.1016/j.atherosclerosis.2009.09.031Get rights and content

Abstract

Background

Coronary artery calcium (CAC) and thoracic aorta calcium (TAC) can be detected simultaneously on low-dose, non-gated computed tomography (CT) scans. CAC has been shown to predict cardiovascular (CVD) and coronary (CHD) events. A comparable association between TAC and CVD events has yet to be established, but TAC could be a more reproducible alternative to CAC in low-dose, non-gated CT. This study compared CAC and TAC as independent predictors of all-cause mortality and cardiovascular events in a population of heavy smokers using low-dose, non-gated CT.

Methods

Within the NELSON study, a population-based lung cancer screening trial, the CT screen group consisted of 7557 heavy smokers aged 50–75 years. Using a case–cohort study design, CAC and TAC scores were calculated in a total of 958 asymptomatic subjects who were followed up for all-cause death, and CVD, CHD and non-cardiac events (stroke, aortic aneurysm, peripheral arterial occlusive disease). We used Cox proportional-hazard regression to compute hazard ratios (HRs) with adjustment for traditional cardiovascular risk factors.

Results

A close association between the prevalence of TAC and increasing levels of CAC was established (p < 0.001). Increasing CAC and TAC risk categories were associated with all-cause mortality (p for trend = 0.01 and 0.001, respectively) and CVD events (p for trend <0.001 and 0.03, respectively). Compared with the lowest quartile (reference category), multivariate-adjusted HRs across categories of CAC were higher (all-cause mortality, HR: 9.13 for highest quartile; CVD events, HR: 4.46 for highest quartile) than of TAC scores (HR: 5.45 and HR: 2.25, respectively). However, TAC is associated with non-coronary events (HR: 4.69 for highest quartile, p for trend = 0.01) and CAC was not (HR: 3.06 for highest quartile, p for trend = 0.40).

Conclusions

CAC was found to be a stronger predictor than TAC of all-cause mortality and CVD events in a high-risk population of heavy smokers scored on low-dose, non-gated CT. TAC, however, is stronger associated with non-cardiac events than CAC and could prove to be a preferred marker for these events.

Introduction

In the past, several studies using both ultrasound and plain radiography have shown an association between calcified plaques in the thoracic aorta (TAC) and cardiovascular and cerebrovascular events [1], [2], [3], [4]. CAC, measured by computed tomography (CT), has proven to be a strong and independent predictor of coronary events and all-cause mortality [5], [6]. Non-enhanced computed tomography (CT) can simultaneously detect both CAC and TAC. Several studies using non-enhanced CT have demonstrated a close association of TAC and CAC [7], [8], [9], [10], [11]. Based on these results, TAC has recently been suggested as an independent predictor of cardiovascular disease, but only two follow-up studies have been reported on this topic [12], [13]. The intuitive advantage of using TAC instead of CAC lies primarily in the fact that CAC measurement may be hampered by motion artifacts of the beating heart while this will hardly affect TAC measurements. As has recently been suggested [9], TAC could prove to be a substitute of CAC for prediction of cardiovascular events in non-gated CT.

Since the heart and thoracic aorta are both depicted on low-dose CT scans for lung cancer screening, and lung cancer and cardiovascular disease share an increased risk with the prolonged use of tobacco, CAC and TAC measurements could be employed to expand the scope of the screening effort and include estimation of cardiovascular risk of screening subjects as well. Adding these measurements at baseline could lead to improved detection of high-risk individuals and, consequently, improved primary prevention of CVD events through optimized preventive treatment of cardiovascular risk factors. So far, no large follow-up studies have investigated the relationship between TAC and CAC in a cohort of asymptomatic smokers. In this study, we investigated whether TAC, as measured on low-dose, non-gated CT, can be used as an independent predictor of all-cause mortality and cardiovascular events compared with CAC. As a secondary analysis, we compared the role of CAC and TAC for the prediction of coronary and non-cardiac events separately.

Section snippets

Study population

The NELSON study is a randomized controlled population-based trial comprising 15,822 men and women aged 50–75 years. Its overall aim is to investigate the beneficial effects of screening for lung cancer with low-dose CT. In 2003–2004, in three regions in the Netherlands and one region in Belgium all men born between 1928 and 1953 living in 101 distinct municipalities, and all women born between 1930 and 1955 living in the remaining 46 municipalities were invited by mail to participate in this

Statistical methods

Baseline characteristics were summarized for the subcohort and the three different case-groups separately. Categorical variables were compared with a χ2 statistic; continuous variables with the Mann–Whitney U-test. Unadjusted annualized event rates for all-cause mortality and CVD events were calculated per CAC and TAC quartile in the subcohort.

In the subcohort, the association between continuous measures of TAC and CAC was investigated with Spearman's rank correlation. Prevalence of CAC and TAC

Results

Table 1 shows the baseline characteristics of a representative baseline sample (subcohort) and all four event-groups. The subcohort included 808 subjects (671 men, 137 women; mean age, 60 ± 6). Compared with the subcohort, subjects in all four event-groups were more often men (p < 0.0001) and more were classified as having diabetes (7% versus 11–18%; p = 0.001). In subjects from the composite CVD, CHD and non-cardiac event-groups, hypertension was more frequent compared with the subcohort (p < 0.0001).

Discussion

CAC has previously been found to be independently associated with all-cause mortality and cardiovascular events [5], [6]. In the present study, TAC was closely associated with CAC. Although both CAC and TAC were associated with all-cause mortality and CVD events in this population of heavy smokers, risk factor-adjusted hazard ratios were consistently higher for CAC compared with TAC. Furthermore, only CAC was associated with coronary events, whereas TAC – and not CAC – was found to be

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