Extent of Coronary Calcium Predicts Long-term Mortality Risk in Symptom-Free Patients

In asymptomatic patients, the extent of coronary artery calcification (CAC) predicts mortality risk up to 15 years after scanning and improves risk classification when added to cardiovascular risk factors, according to a single-center study published in the July 7 issue of Annals of Internal Medicine.

“[Knowing CAC] scores may help patients with high scores adopt healthier lifestyles, and… may help researchers stratify study patients more effectively,” write Leslee J. Shaw, PhD, of the Emory Clinical Cardiovascular Research Institute (Atlanta, GA), and colleagues.

The researchers examined data on 9,715 asymptomatic patients from the Nashville, TN, area who were referred to a single outpatient clinic for CAC testing as part of a cardiology outreach screening program between 1996 and 1999. CAC was measured using electron beam tomography or multislice CT.

Over a mean follow-up of 14.6 years, records from the National Death Index reported that 936 patients died. The 15-year mortality rate increased as the extent of calcification grew (P < .001): from 3% and 6% for CAC scores of 0 and 1-10, respectively, to a high of 28% for CAC scores of 1,000 or greater. Similarly, corresponding hazard ratios increased from 1.68 for scores of 1-10 to 6.26 for scores of 1,000 or more (P < .001 for all). After adjustment for CAD risk factors, the score remained predictive of long-term mortality (P < .001).

Patients were divided into quartiles according to their predicted risk of 15-year mortality, and increasing CAC scores were associated with higher death risks within each of those groups (P < .001 for all).

Adding the score—with cut points ranging from < 7.5% to ≥ 22.5% mortality—to a model with CAD risk factors led to a categorical net reclassification improvement of 0.21 (95% CI 0.16-0.32), a magnitude deemed “substantial” by the authors. Compared with the model using risk factors alone, the model with CAC added correctly reclassified 27.9% of patients who died during follow-up but incorrectly reclassified 7.4% of survivors to a higher-risk category.

Long-term Data Scarce

Although prior studies have shown a relationship between calcium scores and adverse clinical outcomes in asymptomatic patients, few data are available beyond 5 years of follow-up, Dr. Shaw told TCTMD in a telephone interview.

Because patients who typically undergo some type of cardiovascular screening are middle-aged or “early elderly” and are expected to live for many more years, she said, having longer-term data on the impact of screening provides more insight into lifetime risk.

“One of the most compelling findings is that [asymptomatic patients with CAC scores of 400 or higher] are not low-risk people,” she said. “They are very high risk and can have mortality rates approaching 30% at 15 years. And I think that can be a strong motivator for patients to engage in more healthy lifestyles and be more adherent to their medications, which has previously been shown with calcium scoring.”

Implications for Patients

Indeed, although there is no evidence from RCTs that interventions for patients with high scores will improve long-term clinical outcomes, CAC testing has been associated with changes in patient behavior and management that may influence cardiovascular risk.

In the EISNER study, for example, the average Framingham risk score at 4 years was lower in patients who underwent CAC scanning than in those who received usual care. “It may seem reasonable to emphasize expected long-term risk during patient interactions, [which] may promote improved adherence and lifestyle-modifying behaviors,” the authors write. “Care should also be taken to uncover previously undocumented symptoms that, in the setting of elevated CAC, would prompt symptom-guided evaluation and management.”

However, CAC scanning also has the potential for detrimental effects, they say. Patients with very little calcification, for example, may gain a false sense of security and be less adherent to smoking cessation or treatments for various chronic conditions.

“Thus,” the authors write, “even for patients who are free of CAC on the index examination, guideline-directed treatment and lifestyle-modification approaches remain mainstays of clinical practice for effective long-term risk reduction in patients with cardiac risk factors.”

Dr. Shaw and colleagues acknowledge that the study is hindered by the use of data from a single center, which limits generalizability, and by the fact that calcification was measured only once.

In addition, they write, “only binary risk factor data were available, and the lack of continuous data on blood pressure, glucose, and cholesterol measurements likely resulted in an overestimation of the added value of CAC scoring.”

Note: Coauthor James K. Min, MD, is a faculty member of the Cardiovascular Research Foundation, which owns and operates TCTMD.

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Source: 
Shaw LJ, Giambrone AE, Blaha MJ, et al. Long-term prognosis after coronary artery calcification testing in asymptomatic patients: a cohort study. Ann Intern Med. 2015;163:14-21.

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