Coronary Calcium Goes Beyond CV Risk to Predict a Spate of Other Diseases

There is now more evidence that higher levels of coronary artery calcium (CAC), an accepted marker of increased cardiovascular risk, are also linked to a range of noncardiovascular diseases. According to research published this week, the relationship between higher calcium scores and various diseases, including cancer, kidney disease, and chronic obstructive pulmonary disease (COPD), persisted even in the absence of a coronary heart disease diagnosis.

Coronary calcium “is unlikely to be causally associated with non-CVD,” write Catherine Handy, MD (Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, Baltimore, MD), and colleagues. Even so, it “may reflect lifetime exposure to both measured and unmeasured risk factors shared in common between CVD and non-CVD outcomes.”

From a public health perspective, CAC scores that are currently used to estimate a person’s lifetime risk of cardiovascular disease might actually be useful for understanding an individual’s future disease burden more broadly, senior author on the study, Michael Blaha, MD (Johns Hopkins), explained to TCTMD.

“Coronary calcium is a measure of your risk factor burden over the course of your lifetime, plus your vulnerability to damage due to those risk factors,” he said.

As such, the new findings shouldn’t necessarily drive a change in practice. Rather, he suggested, they provide added rationale for being aggressive with risk factor control in people who stand to benefit the most.

“If your score is very, very high, it’s not like I’m going to say to do anything differently for your cancer risk, other than say: eat well, exercise, and the usual [recommendations],” Blaha said. “It’s just an alert that we need to be really aggressive with those risk factors and get them under control in order to reduce the risk of these outcomes that we know from MESA are more likely to happen.”

The new analysis comes from the Multi-Ethnic Study of Atherosclerosis (MESA), which Blaha noted was comprised of patients who were mostly asymptomatic, with no known CVD. “So the natural history will take you to those potential other conditions, but hopefully if we treat those [risk factors], we can reduce the risk of those conditions, as well as cardiovascular disease,” he said.

More Than Just CVD

Handy et al note that CAC has previously been considered a measure of ‘biologic age,’ with other studies linking very high levels of CAC and cancer. Data supporting a connection with other diseases, however, have been mixed.

For the current study, investigators reviewed calcium scores in subjects from six centers participating in MESA, stratifying them by scores of 0, 1-400, or > 400. Study participants were then followed for a median of 10.2 years, with the primary outcome measure being first noncardiovascular disease diagnosis.

Compared with subjects with CAC scores of 0, those with CAC scores over 400 had increased risks of cancer, chronic kidney disease, pneumonia, COPD, and hip fracture. By contrast, subjects with CAC scores of 0 had decreased risks for most of these same conditions compared with subjects who had higher scores.

No statistically significant association was seen between a score of zero and pneumonia, dementia, or DVT/pulmonary embolism (PE). In the case of DVT/PE and pneumonia, their occurrence is typically acute and more likely to be associated with other reasons for hospitalization, the authors note. As for dementia and hip fracture, the number of cases in the series may have been too low to show a link with CAC. Indeed, Blaha noted, the link between CAC and dementia only narrowly missed statistical significance and has been shown in other studies to be linked with subclinical atherosclerosis.

CAC Use Not Uniform

According to Blaha, use of CAC scoring is highly variable across the United States, despite the ease of getting the measurements during cardiac CT and the fact that coronary calcium finally received guideline endorsement in 2013 for use in patients in whom risk of future cardiovascular disease is uncertain.

He predicts the next guideline update will strengthen the endorsement for measuring CAC, due to the wealth of data that has emerged in recent years, this paper included.

“That’s where this [data] is valuable—it’s really showing how good of a risk integrator calcium is,” Blaha commented. “It’s just so much better than taking a onetime measurement of blood pressure or a onetime measurement of weight or even a onetime measure of cholesterol. It really does look directly at the arteries and measure damage directly, which has implications for risk factor burden over a lifetime and vulnerability. It’s really telling us that along multiple different dimensions, calcium scoring tells us [information] about the patient that we didn’t know before.”

In an accompanying editorial, Mosaab Awad, MD; Parham Eshtehardi, MD; and Leslee J. Shaw, PhD (Emory University, Atlanta, GA), point out that it’s not yet clear whether acting on high calcium scores by intensifying risk factor control actually leads to better outcomes, cardiovascular or otherwise. That said, Handy et al’s study and others support a “far-reaching” role for CAC screening and risk prediction across a range of conditions. 

“Although CAC has not been without its critics and is not supported as a reimbursable procedure,” they write, “its expansive evidence warrants a more thoughtful discussion within the CVD community that this powerful procedure provides valuable information to guide healthcare decision making.”

• Handy CE, Desai CS, Dardari ZA. The association of coronary artery calcium with non-cardiovascular disease from the multi-ethnic study of atherosclerosis. J Am Coll Cardiol Img. 2016;Epub ahead of print.
• Awad M, Eshtehardi P, Shaw LJ. Imaging atherosclerosis for global predictive health and wellness. J Am Coll Cardiol Img. 2016;Epub ahead of print.

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• Zero Calcium Score Provides 15-Year Mortality ‘Warranty’ for Asymptomatic Patients