Physicians' Academy for Cardiovascular Education

Negative risk marker for CVD is useful for clinical decision making

Blaha MJ, et al. Circulation 2016

Negative risk marker for CVD is useful for clinical decision making

A coronary artery calcium (CAC) score of 0 is a strong negative CVD risk marker, and may help avoid lifelong preventive pharmacotherapy for individuals who will probably not benefit from it
Role of Coronary Artery Calcium Score of Zero and Other Negative Risk Markers for Cardiovascular Disease: The Multi-Ethnic Study Of Atherosclerosis (MESA)
Blaha MJ, Cainzos-Achirica M, Greenland P, et al.
Circulation 2016;133:849-858


Candidates for the administration of medications with the objective of CVD prevention are selected based on CV risk factor algorithms [1]. Currently, the CV risk factor algorithms are designed for the identification of high-risk individuals, and depend strongly on age and gender [2]. On the other hand, recent guidelines recommend preventive statin treatment also for individuals at lower CVD risk, leading to a possible overtreatment [3,4]. To avoid overtreatment, negative risk markers can be used, such as the absence of a clinical risk marker, or a negative prognostic test result [5], allowing for the identification of individuals who are less likely to benefit from preventive therapy. One such negative risk marker is the coronary artery calcium (CAC) score that is derived from atherosclerosis imaging tests [6].
In this study, 13 negative risk markers were evaluated, in a cohort of 6,814 participants from the Multi-Ethnic Study of Atherosclerosis [7].  

Main results

  • The mean estimated 10-year atherosclerotic cardiovascular disease (ASCVD) risk was 16.4% for males and 11.2% for females.
  • Normal ankle-brachial index (ABI) and no microalbuminuria were the most prevalent negative risk markers:
- normal ABI was present in 93% of participants
- microalbuminuria was present in 90% of participants
- normal FMD (Flow Mediated Dilation) was present in 36% of participants
- low CIMT (Carotid Intima-Media Thickness) was present in 25% of participants
  • The lowest rate of CVD events was observed in participants with CAC=0 (4.0%), whereas the highest occurred in those with a normal ABI (9.9%). Participants with CAC=0 also had the lowest CHD and hard CHD event rates.  
  • CAC=0 showed the best negative risk marker performance with mean diagnostic likelihood ratios (SD):
- CHD events: 0.36 (0.09) in men and 0.46 (0.12) in women
- CVD events: 0.49 (0.10) in men and 0.59 (0.12) in women
- in high CVD participants: 0.47 (0.08)
- in low CVD participants: 0.67 (0.09)
  • CAC=0 was particularly informative in older ages as well as in those with higher pre-test predicted 10-year ASCVD risk.
  • Among clinical features, the absence of any family history of CHD was the most informative negative risk marker: mean risk factor-adjusted diagnostic likelihood ratios (SD):
- for CVD events 0.81 (0.06)
- for CHD events 0.76 (0.07)


CAC=0, derived from atherosclerosis-imaging tests, showed the best negative risk marker performance for the assessment of future CVD risk, and can be used to guide clinical decision making for the selection of individuals who are not likely to benefit from lifelong preventive pharmacotherapy.

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