'Negative Risk Markers,' Like Low CAC Score, Seen to Sharpen Statin Targeting in Elderly

Megan Brooks

July 04, 2019

Elderly people with low coronary artery calcium (CAC) scores, low galectin-3 levels, and no discernible carotid plaque have "remarkably" low cardiovascular (CV) risk, suggests a new report.

The finding, researchers say, could potentially improve targeting of preventive therapies by sharpening risk-prediction models used to guide management.

In recent guidelines, most elderly people may eventually qualify for lifelong statin therapy, given the influence of age on their estimates of atherosclerotic cardiovascular disease (ASCVD) risk, the report notes.

But, "there is a great opportunity for personalizing preventive therapy in the elderly population by using negative risk markers to identify those who don't need treatment," first author Martin Bodtker Mortensen, MD, PhD, Aarhus University Hospital, Denmark, told theheart.org | Medscape Cardiology.

"Most importantly, our data confirm that absence of subclinical atherosclerosis by imaging has particular value as a negative risk marker and may be key to limiting overuse of primary prevention therapies in older adults," he said.

The analysis was published online July 1 in the Journal of the American College of Cardiology.

"To avoid overtreatment with statins in the elderly, there is a strong need for more individualized risk prediction, with accurate identification of elderly individuals at low [ASCVD] risk despite advancing age," agreed Valentin Fuster, MD, the journal's editor-in-chief and a coauthor on the study, in an accompanying podcast commentary.

The researchers compared the ability of 13 potential negative risk markers to downgrade coronary heart disease (CHD) and CVD risk using data on 5805 adults (mean age, 69; 44% men) from the multiethnic BioImage study. Participants had a mean estimated 10-year ASCVD risk of 16.4% and were followed for a median of 2.7 years.

The candidate negative risk markers were a CAC score of 0; a CAC score of 10 or less; no detectable carotid plaque; no family history; normal ankle-brachial index; test result below the 25th percentile for 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 above the 75th percentile.

A CAC score of 0 or 10 or less (present in 32% and 38% of the cohort, respectively) was the strongest negative risk marker, with a mean diagnostic likelihood ratio (DLR) of 0.20 for CHD in both cases.

That corresponds to an 80% lower risk than expected based on traditional risk-factor assessment, the researchers report. For CVD, mean DLRs were 0.41 and 0.48, for CAC scores of 0 and of 10 or less, respectively.

Galectin-3 below the 25th percentile was the next strongest negative risk marker, with DLRs of 0.44 for CHD and 0.43 for CVD, followed by no carotid plaque (0.39 for CHD; 0.65 for CVD). Results obtained with the other candidate risk markers were "less impressive," the researchers note.

Accurate downward risk reclassification for American College of Cardiology/American Heart Association (ACC/AHA) class I statin eligibility threshold was greatest for a CAC score of 0 and of 10or less, with a binary net reclassification index (NRI) of 0.23 and 0.28, respectively), followed by galectin-3 below the 25th percentile (NRI, 0.14) and no carotid plaque (NRI, 0.08).

"Any of these parameters decreases significantly the risk in this elderly population as assessed by the traditional risk calculator. This questions the appropriateness of treating all with a statin when in fact it's not necessary," said Fuster.

The authors say their findings "should be considered in future iterations of guidelines as a potential tool to reduce unnecessary overtreatment in the growing elderly population."

Whereas the traditional interpretation of risk factor is "inextricably tied to more testing and more treatment, the negative risk factor may be used to justify conservative treatment and less follow-up testing," observe Michael Blaha, MD, MPH, Johns Hopkins University, Baltimore, and coauthors in an accompanying editorial.

The chief takeaway from this study, they write, is that atherosclerosis imaging tests are "perhaps the strongest negative risk factors in cardiovascular medicine today. The results are clinically actionable and should shape our approach to these tests in clinical practice. Fortunately, clinical guidelines have taken notice of this emerging consensus."

For example, they note, the 2018 ACC/AHA prevention guidelines assign a class IIa recommendation for CAC testing in selected adults 40 to 75 years of age who are at borderline to intermediate risk to guide individualized management decisions. The guidelines also say it's reasonable to use CAC to reclassify risk in adults 76 to 80 years of age.

Greater attention to negative risk markers "may be key to limiting potential overuse of primary prevention pharmacotherapies in older adults," the editorialists conclude.

The BioImage study is an industry collaboration funded by Abbott, AstraZeneca, Merck, Phillips, and Takeda. Mortensen and Fuster had no disclosures; conflict of interest statements for the other authors are in the report. Blaha reported no conflicts; disclosures for the other editorialists are in the article.

J Am Coll Cardiol. Published online July 1, 2019. Abstract, Editorial

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