Thoracic Aorta Calcification and Noncardiovascular Disease-Related Mortality

Abstract

Objective- Arterial calcification is highly correlated with underlying atherosclerosis. Arterial calcification of the thoracic aorta is evident in many older individuals at high susceptibility to aging-related diseases and non-cardiovascular disease (CVD)-related mortality. In this study, we evaluated the association of thoracic aorta calcification (TAC) with non-CVD morbidity and mortality. Approach and Results- We analyzed data from participants in the Multi-Ethnic Study of Atherosclerosis, a prospective cohort study of subclinical atherosclerosis, in which participants underwent cardiac computed tomography at baseline and were followed longitudinally for incident CVD events and non-CVD events. Using modified proportional hazards models accounting for the competing risk of CVD death and controlling for demographics, CVD risk factors, coronary artery calcium, and CVD events, we evaluated whether TAC was independently associated with non-CVD morbidity and mortality. Among 6765 participants (mean age, 62 years), 704 non-CVD deaths occurred for a median follow-up of 12.2 years. Compared with no TAC, the highest tertile of TAC volume was associated with a higher risk of non-CVD mortality (hazard ratio, 1.56; 95% confidence interval, 1.23-1.97), as well as several non-CVD diagnoses, including hip fracture (2.14; 1.03-4.46), chronic obstructive pulmonary disease (2.06; 1.29-3.29), and pneumonia (1.79; 1.30-2.45), with magnitudes of association that were larger than for those of coronary artery calcium. Conclusions- TAC is associated with non-CVD morbidity and non-CVD mortality, potentially through a pathway that is unrelated to atherosclerosis. TAC may be a general marker of biological aging and an indicator of increased risk of non-CVD and death.

Keywords: aging; aorta, thoracic; atherosclerosis; mortality; tomography.

Figure 1

Conceptual framework for the associations of biological aging, arterial calcification, and non-CVD mortality. Calcification of the arterial wall is a well-recognized consequence of atherosclerosis. We hypothesized that biological aging may also result in arterial calcification through a parallel pathway. While atherosclerosis leads to cardiovascular disease (CVD) events, biological aging may lead to an increased susceptibility to non-CVD events (e.g. cancer), leading to non-CVD related mortality. Aging is also a risk factor for atherosclerosis, which in turn leads to CVD events that can also increase an individual’s susceptibility to non-CVD mortality (e.g. heightened cancer mortality among individuals with a history of clinical CVD).

Figure 2

Kaplan-Meier estimates of freedom from non-CVD mortality stratified by prevalence of TAC, CAC, neither, or both (left) and TAC volume tertile (right). CAC=coronary artery calcium, CVD=cardiovascular disease, TAC=thoracic aorta calcium.

Figure 3

Associations of TAC and CAC with mortality and incident morbidities. Causes of death were adjudicated by physician committee. Morbidities were abstracted from inpatient medical records via International Classification of Diseases, Ninth Edition (ICD-9) codes. Sub-hazard ratios are plotted for tertile 3 of TAC volume and CAC volume compared to a reference of no TAC and CAC volume, respectively. Associations are adjusted for age, sex, race/ethnicity, CVD risk factors (total cholesterol, HDL-cholesterol, systolic blood pressure, hypertension medication, smoking, diabetes mellitus, statin medication, and BMI) and mutually-adjusted for TAC and CAC volume tertile, and nonfatal CVD events. Participants reporting a history of a given morbidity at the baseline examination were excluded from the analysis of that morbidity. Asterisk indicates a p-value <0.05.