Role of Coronary Artery Calcium Score of Zero and Other Negative Risk Markers for Cardiovascular Disease: The Multi-Ethnic Study Of Atherosclerosis (MESA)
Background—Limited attention has been paid to negative cardiovascular disease (CVD) risk markers despite their potential to improve medical decision-making. We compared thirteen negative risk markers using diagnostic likelihood ratios (DLR), which model the change in risk for an individual after the result of an additional test.
Methods and Results—We examined 6,814 participants from the Multi-Ethnic Study of Atherosclerosis. 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 (hsCRP) <2 mg/L, homocysteine <10 µmol/L, NTpro-BNP <100 pg/mL, no microalbuminuria, no family history of coronary heart disease (CHD) (any/premature), absence of metabolic syndrome, and healthy lifestyle were compared for all, hard CHD and all CVD events over 10-year follow-up. Models were adjusted for traditional CVD risk factors. Among all negative risk markers CAC=0 was the strongest, with adjusted mean DLR (SD) 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). HsCRP <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 (NRI) analyses yielded similar findings, with CAC=0 resulting in the largest, most accurate downward risk reclassification.
Conclusions—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.
- Received July 15, 2015.
- Revision received December 23, 2015.
- Accepted January 14, 2016.