The Association of Coronary Artery Calcium With Noncardiovascular Disease: The Multi-Ethnic Study of Atherosclerosis

Abstract

Objectives: This study sought to determine if coronary artery calcium (CAC) is associated with incident noncardiovascular disease.

Background: CAC is considered a measure of vascular aging, associated with increased risk of cardiovascular and all-cause mortality. The relationship with noncardiovascular disease is not well defined.

Methods: A total of 6,814 participants from 6 MESA (Multi-Ethnic Study of Atherosclerosis) field centers were followed for a median of 10.2 years. Modified Cox proportional hazards ratios accounting for the competing risk of fatal coronary heart disease were calculated for new diagnoses of cancer, pneumonia, chronic obstructive pulmonary disease (COPD), chronic kidney disease (CKD), deep vein thrombosis/pulmonary embolism, hip fracture, and dementia. Analyses were adjusted for age; sex; race; socioeconomic status; health insurance status; body mass index; physical activity; diet; tobacco use; number of medications used; systolic and diastolic blood pressure; total and high-density lipoprotein cholesterol; antihypertensive, aspirin, and cholesterol medication; and diabetes. The outcome was first incident noncardiovascular disease diagnosis.

Results: Compared with those with CAC = 0, those with CAC >400 had an increased hazard of cancer (hazard ratio [HR]: 1.53; 95% confidence interval [CI]: 1.18 to 1.99), CKD (HR: 1.70; 95% CI: 1.21 to 2.39), pneumonia (HR: 1.97; 95% CI: 1.37 to 2.82), COPD (HR: 2.71; 95% CI: 1.60 to 4.57), and hip fracture (HR: 4.29; 95% CI: 1.47 to 12.50). CAC >400 was not associated with dementia or deep vein thrombosis/pulmonary embolism. Those with CAC = 0 had decreased risk of cancer (HR: 0.76; 95% CI: 0.63 to 0.92), CKD (HR: 0.77; 95% CI: 0.60 to 0.98), COPD (HR: 0.61; 95% CI: 0.40 to 0.91), and hip fracture (HR: 0.31; 95% CI: 0.14 to 0.70) compared to those with CAC >0. CAC = 0 was not associated with less pneumonia, dementia, or deep vein thrombosis/pulmonary embolism. The results were attenuated, but remained significant, after removing participants developing interim nonfatal coronary heart disease.

Conclusions: Participants with elevated CAC were at increased risk of cancer, CKD, COPD, and hip fractures. Those with CAC = 0 are less likely to develop common age-related comorbid conditions, and represent a unique population of "healthy agers."

Keywords: aging; biologic aging; cancer; coronary artery calcium; coronary artery disease.

Figure 1

Proportion of participants within each coronary artery calcium (CAC) score stratum with any new non-cardiovascular disease (CVD) diagnosis and by each specific diagnosis. Blue bars represent CAC scores=0, the red bars represent CAC scores of 1 – 400, and green bars represent CAC scores >400. (CKD = chronic kidney disease; COPD=chronic obstructive pulmonary disease; DVT=deep vein thrombosis; PE=pulmonary embolism)

Figure 2

Proportion of participants with any non-cardiovascular disease (CVD) diagnosis along with unadjusted (model 1) and multivariable adjusted (model 5) Cox proportional hazard ratios, adjusted for the competing risk of fatal coronary heart disease (95% confidence intervals). Multivariable model was adjusted for age (best fit, see methods), gender, race, socioeconomic status (SES), health insurance status, smoking status and pack years of smoking, body mass index (BMI), physical activity, diet, total number of medications used, systolic and diastolic blood pressure, anti-hypertensive medication use, total and HDL (high density lipoprotein) cholesterol, lipid lowering medication and aspirin use and presence of diabetes.