Role of Coronary Artery Calcium Score of Zero on CVD

Study Questions:

What is the utility of negative (low risk) values for traditional cardiovascular disease (CVD) risk factors and nontraditional CVD risk markers?


The authors used the MESA (Multi-Ethnic Study of Atherosclerosis) study results in 6,814 participants to compare 13 negative risk markers using diagnostic likelihood ratios (DLRs), which model the change in risk for an individual after the result of an additional test. The negative markers included a coronary artery calcium (CAC) = 0, carotid intima-media thickness (CIMT) <25th percentile, absence of carotid plaque, brachial flow-mediated dilation >5% change, ankle brachial index (ABI) >0.9 and <1.3, high-sensitivity C-reactive protein (hs-CRP) <2 mg/L, homocysteine <10 μmol/L, N-terminal pro–B-type natriuretic peptide <100 pg/ml, no microalbuminuria, no family history of coronary heart disease (CHD) (any/premature), absence of metabolic syndrome, and healthy lifestyle. CVD events were defined as hard CHD and all CVD events over 10-year follow-up. Models were adjusted for traditional CVD risk factors and included the ability of each test to accurately move individuals from >7.5% and >5.0% to lower risk. The DLR quantifies the change in risk with knowledge of a test result (post-test risk) versus not knowing the result (pretest risk). Values >1 indicate that the test upgrades disease risk, and values <1 indicate that the test downgrades disease risk.


The study was conducted in men and women free from CVD, baseline mean age 62 ± 10 years (range 45-84 years), and follow-up of 10.3 ± 2.3 years. Among all negative risk markers CAC = 0 was the strongest, with adjusted mean DLR (standard deviation) of 0.41 (0.12) for all CHD and 0.54 (0.12) for CVD, followed by CIMT <25th percentile (DLRs 0.65 [0.04] and 0.75 [0.04], respectively). Hs-CRP <2 mg/L and normal ABI had DLRs >0.80. Among clinical features, absence of any family history of CHD was the strongest (DLRs 0.76 [0.07] and 0.81 [0.06], respectively). Net reclassification improvement analyses yielded similar findings, with CAC = 0 resulting in the largest, most accurate downward risk reclassification.


Negative results of atherosclerosis-imaging tests, particularly CAC = 0, resulted in the greatest downward shift in estimated CVD risk. These results may help guide discussions regarding identification of individuals less likely to receive net benefit from lifelong preventive pharmacotherapy.


This study adds to the potential utility of CAC scores, but considering the very low cost of generic statins, the ability to reduce the CVD risk from ≥7.5% to <7.5% or >7.5% to <5% may not have clinical or cost-effective value. It is not clear to what degree the value of a CAC = 0 was influenced by age.

Clinical Topics: Diabetes and Cardiometabolic Disease, Dyslipidemia, Noninvasive Imaging, Prevention, Atherosclerotic Disease (CAD/PAD), Echocardiography/Ultrasound

Keywords: Ankle Brachial Index, Atherosclerosis, Biological Markers, C-Reactive Protein, Carotid Intima-Media Thickness, Coronary Artery Disease, Dyslipidemias, Homocysteine, Life Style, Metabolic Syndrome X, Natriuretic Peptide, Brain, Plaque, Atherosclerotic, Primary Prevention, Risk Factors

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