Coronary Calcium Predicts Array of Noncardiovascular Diseases

Patrice Wendling

March 24, 2016

BALTIMORE, MA — Coronary artery calcium (CAC) is independently associated with multiple age-related chronic diseases, although less so than for CVD itself, new findings from the Multi-Ethnic Study of Atherosclerosis (MESA) suggest.[1]

A CAC imaging score of over 400 was independently associated with cancer, chronic kidney disease (CKD), chronic obstructive pulmonary disease (COPD), and hip fractures.

"This indicates that CAC indeed appears to be a marker of unhealthy aging and accumulated risk, placing individuals at risk for a variety of important diseases," senior author Dr Michael Blaha (Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, Baltimore, MD) told heartwire from Medscape in an email.

On the other hand, patients with a CAC of zero appear to be protected from CVD and other chronic diseases. The relative hazard for a non-CVD event was cut 25% in these "healthy agers" vs those with detectable CAC, according to the report, published earlier this month in the JACC: Cardiovascular Imaging.

"Despite our findings, I don't think CAC will be used clinically to predict non-CVD diseases at this time," Blaha said. "Our research mainly implies that people with high CAC are likely at risk for a variety of diseases, which is useful information for payers, accountable-care organizations, policymakers, and individual physicians."

Study Details

The investigators looked at 6814 MESA participants followed for a median of 10.2 years. Non-CVD diagnoses were abstracted from inpatient records by ICD-9 codes.

Half of patients did not have any coronary calcium (CAC 0), 40% had scores of 1 to 400, and 10% had scores greater than 400.

Modified Cox-proportional hazard ratios (HRs) accounting for the competing risk of fatal CHD were calculated for new diagnoses of cancer and other conditions.

Analyses were adjusted for age, gender, 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 HDL cholesterol, diabetes, and use of antihypertensive, aspirin, and cholesterol medications.

After full adjustment, patients with a CAC score of over 400 were 53% more likely than those with a CAC of zero to develop cancer (HR 1.53; 95% CI 1.18–1.99).

Risk was also increased for CKD (HR 1.70; 95% CI 1.21–2.39), pneumonia (HR 1.97; 95% CI 1.37–2.82), COPD (HR 2.71; 95% CI 1.60–4.57), and hip fracture (HR, 4.29; 95% CI 1.47–12.50).

A CAC over 400 was not significantly associated with dementia or deep-venous thrombosis/pulmonary embolism (DVT/PE). This may be because they had too few dementia cases and DVT/PE may have more acute-onset risk factors such as trauma and surgery, the group reported.

Lead author Dr Catherine Handy (Johns Hopkins) urged caution in overstating the findings for hip fracture because of small case numbers, but said even they were surprised by what they found for COPD and cancer.

"Cancer was very surprising, and actually the question that I get asked most about is the association between coronary calcium and cancer, and why would those two things be related at all," she told heartwire .

Underlying Mechanisms

CAC is unlikely to be causally associated with non-CVD outcomes, but may be a "risk integrator" that reflects measured and unmeasured risk factors that accumulate over a lifetime, Handy said.

CAC also independently predicts all-cause mortality, which could be driven by CVD and select non-CVD events.

Drs Mosaab Awad, Parham Eshtehardi, and Leslee Shaw (Emory University, Atlanta, GA) write in an accompanying editorial[2] that "the strongest connection between CAC and all of these stated non-CVD conditions is age."

CAC is known to increase with age in prevalence and extent, as are CVD and other non-CVD conditions like COPD, cancer, and dementia.

Further, when the analysis was limited to MESA participants younger than 65 years, none of the non-CVD end points were significantly associated with age. "Thus, the heavy burden of these conditions in the elderly appeared to be the primary impetus for the modeling results," the editorialists write.

Participants with a CAC of zero were also significantly younger than those with a CAC of 1 to 400 or over 400 (57.97 vs 65.32 vs 70.50, P<0.001), which also supports the role of aging in the findings, Dr Robert Eckel (University of Colorado Denver, Aurora), told heartwire .

"I'm underwhelmed, but interested," he said of the study. "I just think this type of thing needs to be validated. It just is so unexpected and would require a mechanistic explanation before one could continue to beat the drum for this issue."

What Now?

Handy said it is unclear how much CAC adds to traditional blood tests and data on age, smoking, and blood pressure in terms of risk assessment for age-related non-CVD conditions.

Critics of CAC for the assessment of CVD risk also argue that the scans increase radiation exposure and can lead to unnecessary and costly downstream testing. That said, "There is certainly no blood test that can predict cancer or CKD; that doesn't exist," she added.

Handy, an oncology fellow, said it is too early to say what role CAC should have in cancer screening, but that they plan to start looking at whether CAC affects treatment decisions, how patients tolerate therapy, and its implications for cancer mortality. Also unknown is whether differential screening should be used, with some people needing to be screened more and others less based on their coronary risk.

Invited to comment, past American College of Cardiology president Dr Anthony DeMaria (University of California, San Diego) told heartwire that the explanation of vascular aging makes sense, but he was also skeptical about using CAC scores at this point to screen for non-CVD diseases. "I think screening is best done when some intervention can take place that can ameliorate the risk that is identified. Here, I can't imagine what interventions can be taken," he said.

MESA was supported by the National Heart, Lung, and Blood Institute and National Center for Research Resources. The authors, editorialists, Eckel, and DeMaria reported no relevant financial relationships.

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