Atherosclerosis Better Predictor of Future Cardiovascular Events Than Stenosis

Critical limb ischemia results in high rates of unplanned hospital readmissions.
Critical limb ischemia results in high rates of unplanned hospital readmissions.
Results of this study contradict the currently held paradigm of stenosis-related CVD risk.

Patients with increased calcified atherosclerosis burden, regardless of coronary artery disease (CAD) obstruction status, had similar risk for cardiovascular disease (CVD) events. These findings from a cohort study were published in the Journal of the American College of Cardiology.

Researchers from the Aarhus University Hospital in Denmark analyzed data from the Western Denmark Heart Registry for this study. All adult patients (N=23,759) who underwent a computed tomography angiography between 2008 and 2017 for a CAD assessment were included. Rates of major CVD and mortality were compared.

Patients were 44.6% men, aged median 57.4 (interquartile range [IQR], 49.7-65.1) years, with median systolic blood pressure of 132 (IQR, 113-148) mmHg, body mass index of 26.2 (IQR, 23.6-29.3) kg/m2, 45.7% had comorbid hypertension, and 8.5% had diabetes mellitus. Patients with (n=5043) or without (n=18,716) obstructive disease differed significantly for all baseline characteristics (all P <.001).

After a median follow-up time of 4.3 (IQR, 2.4-6.1) years, 1054 patients had their first major CVD event (myocardial infarction: n=219; stroke: n=299; death: n=536).

Stratified by coronary artery calcium (CAC) scores, 87% of patients with a score of 0 were CAD-free, and 7% and 6% had nonobstructive and obstructive CAD, respectively. Patients who had a CAC score greater than 1000 were at increased risk for CAD, in which 3% were CAD-free, 14% had nonobstructive CAD, and 83% had obstructive CAD. Most patients with obstructive CAD had CAC scores between 100 and 399.

The risk for major CVD events increased in a stepwise pattern with CAC scores. Compared with patients who had a CAC of 0, those with a CAC of 1 to 99 corresponded with a hazard ratio (HR) of 1.3 (95% CI, 1.1-1.5), those with a CAC of 100 to 399 with HR 1.7 (95% CI, 1.4-2.1), CAC 400-1000 with HR 2.6 (95% CI, 2.1-3.2), and those with a CAC greater than 1000 with HR 3.4 (95% CI, 2.5-4.6).

This observed pattern was similar to that of vessel obstruction, in which compared with no CAD, patients with nonobstructive CAD had an HR of 1.3 (95% CI, 1.1-1.6), 1-vessel CAD with HR 1.6 (95% CI, 1.3-1.9), 2-vessel CAD with HR 1.9 (95% CI, 1.5-2.4), and 3-vessel CAD with HR 2.9 (95% CI, 2.2-3.9).

Among patients with a CAC of 1 to 99, patients with obstructive CAD had increased risk for CVD events (HR, 1.3; 95% CI, 1.0-1.6). However, this risk decreased as CAC increased. Among patients with a CAC greater than 1000, patients with obstructive CAD had a decreased risk for CVD events (HR, 0.6; 95% CI, 0.3-1.1).

This study was limited by its observational design and the fact that the investigators did not have access to other atherosclerotic markers.

These findings suggested the best predictor of future CVD would be current coronary atherosclerotic plaque burden rather than stenoses. This study indicated additional study was needed because these results contradicted the currently held paradigm of stenosis-related CVD risk.

Disclosure: One study author declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of disclosures.


Mortensen MB, Dzaye O, Steffensen FH, et al. Impact of plaque burden versus stenosis on ischemic events in patients with coronary atherosclerosis. J Am Coll Cardiol. 2020;76(24):2803-2813. doi:10.1016/j.jacc.2020.10.021