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

In asymptomatic patients, the absence of detectable coronary artery calcium (CAC) on a CT scan signals at least 15 years of minimal annual mortality risk, according to a study published online July 15, 2015, ahead of print in JACC: Cardiovascular Imaging.

The findings have “high clinical importance,” assert James K. Min, MD, of NewYork-Presbyterian/Weill Cornell Medical Center (New York, NY), and colleagues.

“Given the 15-year warranty of a CAC score of 0 for individuals at low-to-intermediate clinical risk…, use of CAC may be instrumental for avoiding unnecessary testing, even in individuals generally considered at higher risk of unexpected adverse clinical events,” they write.

The investigators looked at data from 9,715 asymptomatic patients without known CAD who underwent CAC screening with electron-beam CT at a single site between 1996 and 1999. All had been referred by their physicians for CAD evaluation. Of this cohort, 4,864 people (mean age 52.1 years; 57.9% men) had a CAC score of 0.

Compared with those without detectable calcium, patients with CAC scores greater than 0 more commonly had hypertension, dyslipidemia, and diabetes. They were also more likely to be smokers and to have a family history of premature CAD and higher Framingham and National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) risk scores.

At a mean follow-up of 14.6 years, 9.6% of patients had died; mortality rates were 4.7% in those with a CAC score of 0 and 14.6% in those with a score greater than 0.

Absence of CAC the Strongest Mortality Predictor

Calcium-free patients had a higher survival rate than those with CAC (95.1% vs 83.7%; P < .001). On multivariable analysis, a CAC score greater than 0 was the strongest predictor of mortality (HR 2.67; 95% CI 2.29-3.11). The risk increased proportionally with the severity of the CAC score but independently of the Framingham and NCEP ATP III risk scores. Findings were similar for men and women. 

At 4.7%, 15-year cumulative mortality for patients with no CAC was lower than the approximately 6% rates for those deemed low risk by the Framingham and NCEP ATP III scores and those with no cardiovascular risk factors. Mortality was lower for those with a CAC score of 0 but at high cardiovascular risk as assessed by standard measures than for patients with evidence of calcification but at low cardiovascular risk.

A  CAC score of 0 was associated with a mortality warranty—defined as annual mortality under 1%—longer than 15 years, with the observed annual rate climbing noticeably after the twelfth year. This mortality rate held true for multiple subgroups, including patients at both low and intermediate risk on Framingham and NCEP ATP III models.  The warranty period was shorter—5 to 6 years—for those at high risk, although it was longer in high-risk patients with no calcium than in low-to-intermediate risk patients with CAC.

Lack of calcification also conferred a lower “vascular age” compared with chronological age, with the difference more pronounced in older patients. For example, a man at least 80 years old with no CAC has a vascular age equivalent to that of a 50-year-old man in the general population, based on observed annual morality rates. 

Moreover, addition of the CAC score incrementally improved the predictive value of the Framingham and NCEP ATP III scores (both P < .001) and resulted in reclassification of events and nonevents in individuals (both P < .001) and a net improvement in risk reclassification regardless of risk category (all P < .001).

An Impetus to Change ‘Preventive Practices’  

The fact that about half of this cohort—in which roughly 50% of people were classified as intermediate or high risk by conventional clinical risk measures—had a CAC score of 0 is not unusual, Robert S. Schwartz, MD, of the Minneapolis Heart Institute Foundation (Minneapolis, MN), told TCTMD in a telephone interview. “You can have ridiculously bad risk factors and yet have no disease as manifested by calcium,” he said. “And conversely, you can have low Framingham scores and have an MI. So I think this is a big step forward in the direction of personalized medicine.”

Due to some early hype, CAC testing has suffered from a bad reputation that has “hampered a lot of good work in the calcium arena,” Dr. Schwartz commented. “Yet the data [about its predictive power] are there. It’s nice to see it coming out in good-quality papers.”

A CAC score of 0 provides “considerable reassurance,” Dr. Schwartz noted. And in his experience, it has not influenced patients to slack off in efforts to pursue a healthy lifestyle, he reported.

The study’s biggest implications are for preventive practices, Dr. Schwartz asserted. These data “question the way statins and now the PCSK9 inhibitors have been sold. With a 0 CAC score, you don’t have to treat the cholesterol, you treat the individual. I think this [study] gives impetus to a practice of not starting statins in these patients and perhaps taking them off the drugs if they have already been started. That’s a huge part of the national medical expenditure, and it’s probably unnecessary.”

The study authors caution that because the CAC score applies only to the coronaries and not to other vascular territories, “the present results should not be interpreted as supporting a practice of therapy diminution or cessation.” However, Dr. Schwartz attributed this statement largely to methodological—and political—correctness.

A CAC score of 0 also reduces the likelihood of downstream testing, Dr. Schwartz said. “Frequently, people [with other risk factors] get a treadmill test, a stress nuclear or stress echo, and with a minor abnormality, it can set off a cascade that ends up in the cath lab. And that’s completely unnecessary. I think this will put a stop to that waste of time, money, and worry.”

Current CT guidelines support performing calcium scans in intermediate-risk patients, Dr. Schwartz noted, but “now we’re talking about preventive guidelines, which are a much bigger piece of the pie, and that’s where making inroads is difficult. But this needs to be spread out into preventive practices.”

Note: Dr. Min is a faculty member of the Cardiovascular Research Foundation, which owns and operates TCTMD.