CAC of Zero? Try to Keep It That Way

Coronary artery calcium (CAC) is a known risk factor for cardiovascular (CV) disease, even if clinicians maybe confused about how best to use the test. The higher a patient’s score on a CAC scan, the worse their prognosis. But what can clinicians tell patients whose arteries are clear of calcium build-up? 

A new study suggests patients with a CAC of 0 can keep it that way by optimizing their overall CV health through diet, exercise, and other modifiable risk factors. In turn, maintaining a CAC of 0 or near 0 could prevent or delay the onset of progressive atherosclerosis.

“Having better control of risk factors like blood sugar, blood pressure, and cholesterol, may prolong the time that people live with a CAC score of zero,” said Nilay S. Shah, MD, an assistant professor of cardiology, preventive medicine, and medical social sciences at Feinberg School of Medicine, Northwestern University, in Chicago, who led the study.

“I think the takeaway is that optimizing cardiovascular health with better cardiovascular risk factor control may delay the onset of coronary artery calcium as a marker of the development and advancement of atherosclerosis,” Shah added.

Multi-Ethnic Study of Atherosclerosis (MESA) Generates New Data

The data were drawn from the MESA, an ongoing look at how CV disease develops and progresses in Black, Chinese, Hispanic, and White adults of ages 45 years through 84 years.

Of the 3416 participants with a CAC score of 0 at enrollment, CV health was calculated with the American Heart Association’s Life’s Simple 7 risk assessment: smoking, physical activity, dietary quality, BMI, cholesterol, blood glucose, and blood pressure.

On the basis of cumulative scores for all seven risk factors, 911 (27%) patients met criteria for a high level of CV health, 2154 (63%) met criteria for intermediate level of CV fitness, and 351 (10%) had a low level of CV health.

Of participants in the study, recently published in JACC: Cardiovascular Imaging, 44.5% were Black individuals, 29.7% were Hispanic individuals, 22.1% were White individuals, and 3.7% were Chinese. The median follow-up was 9 years. About 63.5% were women and about 25% were older than age 65 years.

Among patients of ages 45-64 years, the survival curves for a CAC of 0 began to separate at 2 years for the three levels of CV health. By the end of follow-up, those with a high level of CV health at baseline maintained a CAC score of 0 for about 1.5 years longer on average (P <.01) than those with a low health at baseline. For those in the intermediate group, survival with a CAC score of 0 was about 1 year longer (P <.01) than those with low level of CV fitness at baseline.

However, this separation of curves was not observed in patients older than 65 years, Shah and his colleagues reported. In these people, having a high, relative to an intermediate or low, level of CV health at baseline did not increase the amount of time someone would maintain a calcium score of 0.

Sub: Sex Difference Observed

The separation of the curves for the three levels of CV health at baseline differed in men. Those with a high level of CV health at baseline fared much better than those at low risk and even those at intermediate risk in terms of how long they maintained a CAC score of 0. That trend held even when they maintained a CAC score of 0 longer than those with a low level of CV health at baseline, according to the researchers.

In women, however, high, low, and intermediate levels of CV health correlated with distinct and statistically significant differences in sustained 0 CAC scores.

The study did not measure hard outcomes, such as CV events, but MESA data published in 2015 found CAC scores > 100 are associated with sevenfold to 10-fold greater risk for atherosclerotic CV disease, whereas CAC scores of 0 are associated with a 4.5% lower rate of events than predicted, according to Shah.

A secondary analysis of the more recent MESA data did show a difference in survival with a CAC score of 0 across specific components of baseline CV health, including dietary quality, cholesterol, blood pressure, and fasting glucose, among younger study participants, but not in individuals over age 65.

MESA showed maintaining a calcium score of 0 reduced subsequent risk for developing CV problems. So does the new data support testing for CAC at a relatively young age? 

Shah was hesitant to endorse that approach. “I do not think that a baseline calcium score in young individuals in the 30s or early 40s is likely to be clinically useful,” he said. “The prevalence of a CAC score > 0 is very low in this age group. I would posit that more comprehensive scoring at those ages would result in a lot of population radiation exposure without a lot of CAC detected.”

But Matthew Budoff, MD, a professor of medicine at the University of California Los Angeles and an endowed chair of preventive cardiology at the Lundquist Institute, in Torrance, California, disagreed. Two years ago, Budoff was a senior author of a state-of-the-art review on CAC guidelines.

Depending on the guideline, “the recommended age for CAC for patients with a family history of CV disease is 38 years old in men and about 48 years old in women,” said Budoff, noting these numbers have been validated in studies from large consortiums.

He also disagreed radiation exposure due to a calcium scan is meaningful in patients with risk factors for CV disease. The exposure for a CAC scan is about the same as that from a mammogram, which is widely regarded as acceptable for catching breast cancer at an early stage. Yet he said heart disease kills about 10 times more women each year.

According to the review of CAC guidelines for which Budoff was a co-author, the common thread is that calcium scoring is helpful to up- or down-classify the risk status of patients assessed on the basis of conventional variables, such as elevated blood pressure or blood glucose. While a high score might lead to more intensive therapy in patients with modest elevations in conventional risk factors, a low score signals a low relative risk for events even among those with other factors, such as a family history, that might cause concern.

The value of identifying a CAC score of 0 and offering strategies to maintain CV health in order to keep the score low is implied but has not been established by Shah’s study.

Budoff did not comment specifically on the implications of a CAC score of 0. However, he said elevated CAC is useful in the context of other risk factors to consider more or less intensive intervention, and the score can help guide therapy in patients with intermediate risk on conventional variables.

The gene or genes that determine the risk of elevated CAC scores are not well understood, but Budoff said the phenotype of elevated calcium has been well defined. He argued for “aggressive therapy” when a calcium score is above the 75th percentile for age and sex in a patient with major risk factors for CV disease.

Shah and Budoff reported no relevant financial conflicts of interest.