Role of Coronary Artery Calcium Score of Zero and Other Negative Risk Markers for Cardiovascular Disease: The Multi-Ethnic Study of Atherosclerosis (MESA)
Michael J Blaha, Miguel Cainzos-Achirica, Philip Greenland, John W McEvoy, Ron Blankstein, Matthew J Budoff, Zeina Dardari, Christopher T Sibley, Gregory L Burke, Richard A Kronmal, Moyses Szklo, Roger S Blumenthal, Khurram Nasir - Circulation, 2016
Among 13 negative ("downward-shifting") cardiovascular risk markers in a multi-ethnic cohort, a coronary-artery calcium score of zero (CAC=0) was the single strongest, producing the largest downward shift in estimated risk (adjusted mean diagnostic likelihood ratio 0.41 for all coronary heart disease and 0.54 for all cardiovascular disease over 10 years), ahead of carotid intima-media thickness below the 25th percentile. This quantifies the popularized "power of zero": a negative imaging test, especially CAC=0, confers low short-to-intermediate-term risk. Whether to withhold preventive therapy on that basis is a separate question this paper does not settle.
Key findings
- Among 13 negative ("downward-shifting") CVD risk markers in 6814 MESA participants free of baseline CVD and followed for about 10 years, a coronary-artery calcium score of zero (CAC=0) was the single strongest.
- CAC=0 produced an adjusted mean diagnostic likelihood ratio (DLR) of 0.41 (SD 0.12) for all coronary heart disease and 0.54 (SD 0.12) for all cardiovascular disease - the largest downward shift in estimated risk.
- The next-strongest negative marker, carotid intima-media thickness below the 25th percentile, gave DLRs of 0.65 (SD 0.04) for CHD and 0.75 (SD 0.04) for CVD.
- A negative imaging test, particularly CAC=0, produced the greatest downward shift in estimated CVD risk - the basis of the popularized "power of zero."
Effect measures
- Other: Diagnostic likelihood ratio (DLR) 0.41 (SD 0.12)
- Other: Diagnostic likelihood ratio (DLR) 0.54 (SD 0.12)
- Other: Diagnostic likelihood ratio (DLR) 0.65 (SD 0.04) for CHD and 0.75 (SD 0.04) for CVD
Why this evidence tier (High)
- Risk of bias:
- Prospective MESA cohort free of baseline CVD with about 10-year follow-up and a prespecified comparison of 13 negative risk markers via diagnostic likelihood ratios. Observational prognostic design.
- Precision:
- Large cohort with long follow-up; DLR estimates are tight (e.g. CAC=0 DLR 0.41, SD 0.12).
- Directness:
- Directly quantifies how much a negative imaging test shifts estimated CHD/CVD risk in a primary-prevention population.
- Consistency:
- Concordant with Detrano 2008 and the wider CAC literature on the prognostic value of a zero score.
- Funding / COI:
- Disclosures: None stated. Supported by NHLBI (contracts N01-HC-95159 through N01-HC-95169) and NCRR grants UL1-TR-000040 and UL1-TR-001079; one author funded by a Spanish Society of Cardiology grant.
High certainty that a zero calcium score is the strongest negative risk marker for short-to-intermediate-term CHD/CVD; whether to withhold preventive therapy on that basis is a separate, broader-literature question this paper does not settle.
- Population:
- 6,814 participants from the Multi-Ethnic Study of Atherosclerosis (MESA), a multi-ethnic cohort free of clinical cardiovascular disease at baseline, followed for about 10 years.
- Conflicts of interest:
- Disclosures: None stated. Funding from NHLBI (contracts N01-HC-95159 through N01-HC-95169) and NCRR grants UL1-TR-000040 and UL1-TR-001079; Miguel Cainzos-Achirica was funded by a research grant from the Spanish Society of Cardiology. No retraction or erratum was found.
- Funding:
- NHLBI (contracts N01-HC-95159 through N01-HC-95169) and NCRR grants UL1-TR-000040 and UL1-TR-001079; one author supported by a Spanish Society of Cardiology research grant.
Limitations
- Observational cohort: it quantifies risk re-estimation, not whether acting on CAC=0 (e.g. withholding statins) improves outcomes.
- The DLRs apply over about 10 years; a zero score is not a guarantee of long-term safety.
- Claims that CAC=0 identifies people less likely to benefit from lifelong preventive pharmacotherapy go beyond this paper and come from the broader CAC literature and editorials, not from this study.