Very High Coronary Artery Calcium (≥1000) and Association With Cardiovascular Disease Events, Non-Cardiovascular Disease Outcomes, and Mortality: Results From MESA.
Level 3 - non-randomized controlled study
Prospective observational cohort study with multivariable adjustment
PubMed 33650435 · doi:10.1161/CIRCULATIONAHA.120.050545
What was done
Researchers analyzed 6,814 ethnically diverse adults aged 45 to 84 years free of baseline cardiovascular disease (CVD) from the Multi-Ethnic Study of Atherosclerosis (MESA) over a mean follow-up of 13.6 ± 4.4 years. Using multivariable Cox proportional hazards models adjusted for age, sex, and traditional risk factors, they evaluated the associations of very high coronary artery calcium (CAC ≥1000) versus CAC 0 and CAC 400–999 with CVD events, non-CVD outcomes, and all-cause mortality. They also modeled annualized event rates to compare MESA participants with the placebo group of the FOURIER secondary prevention trial.
What was found
Participants with CAC ≥1000 (n=257) had more vessels with calcification (3.4 ± 0.5) and greater calcified area (586.5 ± 275.2 mm²) compared to those with CAC 400–999. Fully adjusted hazard ratios (HR) for CAC ≥1000 versus CAC 0 were 4.71 (95% CI, 3.63–6.11) for all CVD, 7.57 (95% CI, 5.50–10.42) for all coronary heart disease (CHD), 4.86 (95% CI, 3.32–7.11) for hard CHD, 1.94 (95% CI, 1.57–2.41) for all-cause mortality, and 1.95 (95% CI, 1.57–2.41) for non-CVD events. Compared to CAC 400–999, CAC ≥1000 carried an HR of 1.65 (95% CI, 1.25–2.16) for all CVD, 1.66 (95% CI, 1.22–2.25) for all CHD, 1.51 (95% CI, 1.03–2.23) for hard CHD, 1.34 (95% CI, 1.05–1.71) for mortality, and 1.43 (95% CI, 1.12–1.83) for non-CVD events. Annualized 3-point major adverse cardiovascular event rates at CAC 1000 reached 3.4 per 100 person-years, matching the overall FOURIER secondary prevention trial rate (3.3 per 100 person-years).
Why it matters
These findings suggest that asymptomatic individuals with CAC ≥1000 face cardiovascular event rates on par with patients with established atherosclerotic disease. This challenges the strict boundary between primary and secondary prevention, supporting intensive pharmacotherapy in this high-risk subset.
Limits
Only 257 individuals had CAC ≥1000, limiting precision for specific subgroups. The study is observational and prone to residual confounding. The comparison to the FOURIER trial relied on cross-study statistical modeling rather than a direct within-trial comparison, and changes in preventive medications during the 13-year follow-up were not accounted for in the abstract.
Cited by
- contradicts A coronary artery calcium score of 1,000 or above often indicates plaque stabilization and calcification associated with lower risk than lower scores with unstable plaque.