Negative Risk Markers for CV Events in Older Adults Identified

elderly man, sitting hands on heart

Elderly people with coronary artery calcium (CAC) of 0, CAC ≤10, low galectin-3 level, or no carotid plaque have a significantly lower risk for cardiovascular disease, according to results published in the Journal of the American College of Cardiology.

The study included participants from the BioImage study, a cohort of elderly men 55 to 80 years of age and women 60 to 80 years of age, who did not have known atherosclerotic cardiovascular disease at baseline (n=5805).

The researchers investigated 13 candidate markers: CAC=0, CAC ≤10, no carotid plaque, no family history, normal ankle-brachial index, test results <25th percentile (carotid intima-media thickness, apolipoprotein B, galectin-3, high-sensitivity C-reactive protein, lipoprotein(a), N-terminal pro-B-type natriuretic peptide, and transferrin), and apolipoprotein A1 >75th percentile. They compared negative risk factor performance using participant-specific diagnostic likelihood ratio (DLR) and binary net reclassification index (NRI).

The results indicated that CAC=0 and CAC≤10 were the strongest negative risk markers. CAC=0 had a mean DLR of 0.20 for coronary heart disease and 0.41 for cardiovascular disease, whereas CAC≤10 had a mean DLR of 0.20 and 0.48, respectively.

Participants with galectin-3 <25th percentile had a mean DLR of 0.44 for coronary heart disease and 0.43 for cardiovascular disease. Those with an absence of carotid plaque had a mean DLR of 0.39 and 0.65, respectively.

The researchers found that results of the other candidate markers were not  significant.

CAC=0 and CAC≤10 had the largest accurate downward risk reclassification across the class I statin-eligibility threshold defined by the American College of Cardiology/American Heart Association (NRI 0.23 and 0.28, respectively). These were followed by galectin-3 <25th percentile (NRI 0.14) and absence of carotid plaque (NRI 0.08).

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“Our results hold the potential to markedly improve statin allocation in elderly individuals by de-escalating or even withholding preventive therapy in elderly individuals at truly low [atherosclerotic cardiovascular disease ] risk despite advancing age,” the researchers wrote.

Disclosure: The BioImage Study was designed by the High-Risk Plaque Initiative, a pre-competitive industry collaboration funded by Abbott, AstraZeneca, Merck, Philips, and Takeda. Multiple authors disclosed affiliations with pharmaceutical companies. See the reference for complete disclosure information.


Mortensen MB, Fuster V, Muntendam P, et al. Negative risk markers for cardiovascular events in the elderly. J Am Coll Cardiol. 2019;74(1):1-11.