Elevated Coronary Artery Calcium Increases Risk of Non-Cardiovascular Disease Diagnosis

First occurrence of non-cardiovascular disease diagnosis in participants with coronary artery calcium score of 0 was 11.0, 22.5% for a CAC score of 1-400, and 36.9% for CAC >400.

Elevated coronary artery calcium (CAC) appears to increase risk of a non-cardiovascular disease (CVD) diagnosis, according to research published in JACC: Cardiovascular Imaging.

While CVD mortality has substantially declined in recent years, non-CVD deaths have not declined at the same rate. Therefore, researchers decided to examine if CAC could be associated with incident non-CVD.

They selected 6184 participants from 6 MESA (Multi-Ethnic Study of Atherosclerosis) field centers, between the ages of 45 and 74 years (mean age: 62 years; 52.9% female) who were free of CVD. Participants were Caucasian (38.5%), African American (27.8%), Hispanic (22%), and Chinese (11.8%), and followed-up for a median of 10.2 years.

The primary outcome was first incident non-CVD diagnosis, including cancer, chronic obstructive pulmonary disease (COPD), chronic kidney disease (CKD), deep vein thrombosis (DVT) or pulmonary embolism (PE), dementia, hip fracture, and pneumonia.

Just over 50% of participants (n=3416) had a CAC score=0, 39.9% (n=2721) had CAC score of 1 to 400, and nearly 10% (n=677) had CAC score of >400. Those with a CAC=0 were more likely to be female, younger, and physically active.

In total, there were 1238 first non-CVD diagnoses. The proportion of first occurrence of any 1 of them was 11.0% for CAC=0, 22.5% for CAC of 1 to 400, and 36.9% for CAC>400 (P<.001).

Cancer had the highest number of non-CVD diagnoses (n=710). Stratified by CAC score, the proportion of participants were as follows: 6.67% for CAC=0, 12.6% for CAC of 1 to 400, and 20.4% for CAC>400 (P<.001). A doubling of CAC score was associated with a 4% increased risk of cancer in multivariable-adjusted models (hazard ratio [HR]: 1.04; 95% confidence interval [CI]: 1.02-1.07), and those with CAC>400 had a 53% greater hazard of cancer compared to those with CAC=0 (HR: 1.53; 1.18-1.99).

CKD had the next highest number of diagnoses (n=395). By CAC score, 3.2% of patients had CAC=0 and 13.3% of patients had CAC>400 (P<.001). After adjustment for CVD risk factors, a doubling of CAC score remained significantly associated with increased hazard of diagnosis (HR: 1.07; 95% CI: 1.03-1.10), and those with CAC>400 were 70% more likely to develop CKD compared to those with CAC=0 (HR: 1.70; 95% CI: 1.21-2.39).

DVT or PE occurred in 205 participants. By CAC score, 1.1% of participants had CAC=0, 1.9% had CAC of 1 to 400, and 2.1% had CAC>400 (P<.05). The doubling of CAC score and CAC>400 were associated with increased hazard of DVT or PE in unadjusted models (HR: 1.10; 95% CI: 1.06-1.13 and HR: 2.24; 95% CI: 1.50-3.35, respectively). However, in multivariable adjusted models, this association was lost (HR: 1.03; 95% CI: 0.98-1.08).

Similar patterns were observed in COPD and dementia; 161 participants were diagnosed with COPD, increasing in CAC score stratum from 1.2% (CAC=0) to 5.6% (CAC>400); and 119 participants were diagnosed with dementia, increasing in CAC score stratum from 0.61% (CAC=0) to 4.43% (CAC>400). Only 59 cases of hip fractures were recorded with CAC stratum ranging from 0.26% (CAC=0) to 1.77% (CAC>400).

The large sample, multi-ethnic makeup, detailed baseline risk factor assessment, and use of competing risk model were major strengths of this analysis. Researchers also allowed “flexible modeling of age to achieve the best fit” and therefore limited “residual confounding.”

“Our results support CAC as a marker for other age related diseases and support limited prior findings showing an association between elevated CAC scores and non-CV diseases including cancer and COPD,” the authors wrote. “While CAC has been shown to be associated with all-cause mortality, this association may be driven by both CV and select non-CV causes.”

Finally, people with CAC=0 appear to be protected from CVD as well as other chronic diseases. These “healthy agers,” as researchers labeled them, are at very low risk of CVD and non-CVD mortality and morbidity.


Handy CE, Desai CS, Dardari ZA, et al. The association of coronary artery calcium with non-cardiovascular disease from the Multi-Ethnic Study of Atherosclerosis. JACC Cardiovasc Imaging. 2016. doi:10.1016/j.jcmg.2015.09.020.