CHICAGO – Absence of coronary artery calcium upon imaging results in an impressively low cardiovascular event rate over the next 10 years regardless of an individual’s level of standard risk factors, according to prospective data from the MESA study.

In contrast, a coronary artery calcium (CAC) score of 1-10, often described as minimal CAC, nearly doubles the 10-year risk, compared with a baseline CAC score of 0.

Prior to these new 10-year data, many cardiologists considered a CAC score of 1-10 as tantamount to no CAC. Not so, Dr. Parag H. Joshi said at the American Heart Association scientific sessions.

“A CAC of 0 is presumably identifying someone without any atherosclerosis. Just the presence of minimal calcium suggests that atherosclerosis is building up. Our data suggest that among individuals with a CAC of 1-10, current smoking, elevated non-HDL cholesterol, and particularly hypertension should be treated aggressively,” said Dr. Joshi, a clinical fellow in cardiovascular diseases and prevention at Johns Hopkins University, Baltimore.

Prior studies totaling more than 50,000 subjects with a CAC score of 0 have shown very low cardiovascular event rates over 4-5 years of follow-up. However, current cardiovascular risk estimates focus on 10-year risk. This new analysis from MESA (Multi-Ethnic Study of Atherosclerosis) is the first study to provide prospective, 10-year events data, and those data are highly reassuring, he added.

MESA is a prospective, population-based cohort study. This analysis included 6,814 subjects aged 45-84 who were free of clinical cardiovascular disease at baseline, when their CAC score was determined. At that time, 3,415 participants had a CAC score of 0 and 508 had a score of 1-10.

During a median 10.3 years of follow-up, 123 cardiovascular events occurred, roughly one-third of which were nonfatal acute MIs and half of which were nonfatal strokes; the remainder were cardiovascular deaths.

The event rate was 2.9/1,000 person-years in subjects with a CAC of 0 and significantly greater at 5.5/1,000 person-years with a score of 1-10. However, since the cardiovascular risk factor profile of the zero CAC group was generally more favorable, Dr. Joshi and coinvestigators carried out a Cox proportional hazards analysis factoring in demographics, standard cardiovascular risk factors, body mass index, C-reactive protein level, and carotid intima media thickness. The adjusted 10-year event risk in the group with a CAC score of 1-10 was 1.9-fold greater than with a CAC of 0.

The highest 10-year event rate was noted in subjects with at least three of the following four risk factors at baseline: hypertension, current smoking, diabetes, and hyperlipidemia. The rate was 6.5/1,000 person-years in such individuals if they had a CAC of 0 and doubled at 13.1/1,000 person-years with a score of 1-10.

In a multivariate Cox analysis, age, smoking, and hypertension proved to be significant predictors of cardiovascular events in the group with a CAC of 0 as well as in those with a CAC of 1-10. But there was one important difference between the two groups: While the hazard ratio for cardiovascular events associated with hypertension versus no hypertension was 2.1 in subjects with a CAC of 0, the presence of hypertension in individuals with a CAC of 1-10 increased their event risk by 10.2-fold, or nearly five times greater than the risk increase associated with hypertension in persons with a CAC of 0, Dr. Joshi observed.

Non–HDL cholesterol level was predictive of cardiovascular risk in subjects with a CAC of 1-10 but not in those with a score of 0.

When actual event rates were compared with those predicted by the atherosclerotic cardiovascular disease (ASCVD) risk estimator introduced in the 2013 AHA/American College of Cardiology cholesterol guidelines, the event rate in subjects with an ASCVD 10-year risk estimate of 7.5%-15% but a CAC of 0 was just 4.4%.

Audience members noted that CAC scores didn’t do a very good job of stratifying stroke risk in MESA. That’s not surprising, since the score reflects coronary but not carotid artery calcium. But it is a limitation of CAC as a predictive tool, especially in light of the fact that strokes accounted for half of all cardiovascular events in the study.

Asked where he and his coinvestigators plan to go from here, Dr. Joshi said a randomized, controlled trial would be ideal, but to date funding isn’t available. However, the observational data from MESA and other studies suggest such a trial may not even be needed.

“Certainly the guidelines do allow for CAC scoring to be used in clinical decision making,” he noted.

The MESA study is funded by the National Heart, Lung, and Blood Institute. Dr. Joshi reported having no financial conflicts.

bjancin@frontlinemedcom.com

Zero coronary calcium means very low 10-year event risk