Value of CAC and Net Benefit of Aspirin in Primary Prevention of ASCVD

Quick Takes

  • Increasing CAC is associated with both bleeding and ASCVD risk. A CAC score ≥100 has nearly a threefold increase in bleeding risk and fivefold ASCVD risk of those with a CAC score = 0.
  • Aspirin is of benefit in those with CAC score = 0 only in those with >20% ASCVD risk.
  • Aspirin is net harmful in those with risk <5% regardless of the CAC score and net harmful regardless of CAC score and ASCVD risk in those with increased bleeding risk.

Study Questions:

Can coronary artery calcium (CAC) scores identify persons without atherosclerotic cardiovascular disease (ASCVD) who are most likely to derive benefit from aspirin therapy?


The investigators utilized the Dallas Heart Study, a cross-sectional study of ASCVD risks and imaging from 2000-2002 in Dallas county that transitioned to a longitudinal study with repeat sampling in 2007 and beyond to the present. Investigators defined and obtained major bleeding and ASCVD events from hospital admissions using International Statistical Classification of Diseases, Ninth Revision codes. Meta-analysis–derived aspirin effect estimates were applied to observed ASCVD and bleeding rates to model the net effect of aspirin at different CAC thresholds. Sensitivity analysis used effect estimates of 10% relative risk reduction for ASCVD events and a 39% relative risk increase in major bleeding.


A total of 2,191 participants (mean age 44 years, 1,247 women [57%], and 1,039 blacks [47%]) had 116 major bleeding and 123 ASCVD events over a median follow-up of 12.2 years. Higher CAC categories (CAC scores 1-99 and ≥100 vs. CAC score 0) were associated with ASCVD events (hazard ratio [HR], 1.6; 95% confidence interval [CI], 1.1-2.4; HR, 2.6; 95% CI, 1.5-4.3) and bleeding events (HR, 4.8; 95% CI, 2.8-8.2; p < 0.001; HR, 5.3; 95% CI, 3.6-7.9; p < 0.001), but the association between CAC and bleeding was attenuated after multivariable adjustment. Applying meta-analysis estimates, irrespective of CAC, aspirin use was estimated to result in net harm in individuals at low (<5%) and intermediate (5%-20%) 10-year ASCVD risk and net benefit in those at high (≥20%) ASCVD risk. Among individuals at lower bleeding risk, a CAC score of ≥100 identified individuals who would experience net benefit, but only in those at borderline or higher (≥5%) 10-year ASCVD risk. In individuals at higher bleeding risk, there would be net harm from aspirin irrespective of CAC and ASCVD risk.


Higher CAC is associated with both ASCVD and bleeding events, with a stronger association with ASCVD. A high CAC score identifies individuals estimated to derive net benefit from primary prevention aspirin therapy from those who would not, but only in the setting of lower bleeding risk and estimated ASCVD risk that is not low.


While the findings are helpful using CAC score = 0 and >100 because they are well defined, high bleeding risk is very difficult to assess. Only about 1 in 200 healthy middle-aged adults treated with aspirin have a serious bleed (about 1% for 5 years), which is not limited to hospitalizations. The following help predict major bleeding risk (i.e., gastrointestinal, intracranial, or less common ‘other’) to guide aspirin use for primary prevention in both men and women (Selak V, et al. Ann Intern Med 2019): Asians and Pacific compared to European ancestry, age ≥75; current smoker, diabetes, cancer; prior bleeding; peptic ulcer disease; alcohol-related conditions; chronic liver disease or pancreatitis; and use of medications for peptic ulcer disease, nonsteroidal anti-inflammatory medication, corticosteroids, and selective serotonin reuptake inhibitors. Other established CVD risk factors were not associated with increased risk.

Keywords: Aspirin, Atherosclerosis, Cardiovascular Diseases, Diagnostic Imaging, Hemorrhage, Patient Admission, Plaque, Atherosclerotic, Primary Prevention, Risk Reduction Behavior

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