Coronary calcium by computed tomography and outcomes: Can a test save a life?

Though cardiovascular disease (CVD) remains the number one killer around the globe, our efforts at successfully screening for primary CVD prevention have failed to produce an efficacious test. Routine stress tests, angiograms, laboratory markers, and other assorted metrics have been unable to reliably predict or prevent the incident cardiovascular event in patients—even those at the highest risk.

In this large, claims-based, retrospective analysis comparing patients who underwent coronary artery calcium (CAC) scoring to those who did not, Dr. Miles and colleagues found a “protective” benefit of CAC testing.¹ The authors used a massive patient database consisting of International Classification of Diseases, Tenth Revision (ICD-10) diagnoses and testing or procedural Current Procedural Terminology codes to amass two groups of over 85,000 patients (about the seating capacity of the Los Angeles Memorial Coliseum) without prior CVD who either underwent CAC testing or did not. Despite an inconclusive list of predictors that could be related to CVD events or all-cause mortality, the groups were fairly well matched, young, and with only minimal ICD-10–listed risk factors for CVD events. Only a small minority of the patients were on a statin medication, despite all of them having an ICD-10 diagnosis of hyperlipidemia. To this point, it might be interesting to know how many patients were statin intolerant versus having hyperlipidemia with diet control alone vs those given an incorrect diagnosis of hyperlipidemia. Furthermore, the authors did not report representative lipid values for the patients or changes in metrics over time.

Using simple logistic regression, the authors found a statistically higher rate of myocardial infarction as assessed by ICD-10 code in the cohort that did not undergo CAC testing. Though they noted a relatively robust 44% lower number of events, the risk of myocardial infarctions in those with and without CAC scoring was roughly 0.5% and 1.0% at 5 years. Similarly, the authors found a statistically significant 76% lower all-cause mortality at 5 years in those who underwent CAC testing, with 98% of the patients who underwent computed tomography (CT) calcium scoring surviving at 5 years as opposed to only 95% of those who did not undergo CT calcium scoring surviving at 5 years. Though the authors noted statistical significance using conventional analyses in this large cohort, the clinical significance of these findings or how they might change with more nuanced statistical analyses is unclear.

Notably absent from this analysis are the actual results of the CT calcium scores for both cohorts and whether or not those values predicted either myocardial infarction or all-cause mortality at 5 years. When assessed for 5- to 10-year rates of CVD events,² the majority of patients would have a 5% to 6% rate of a CVD event. This percentage can drop to <3% with a calcium score of 0 and can go up to almost 15% with a calcium score of 500 (90th percentile). Clearly, this cohort is at an even lower risk for multiple reasons, which could include sampling/inclusion or reporting biases. Furthermore, there were no data on the progression of the risk factors known to predict myocardial infarction or all-cause mortality throughout the 5 years in either one of the cohorts. The available data on statins for primary prevention put the number needed to treat at approximately 100 patients,³ which this data set would have the power to detect if the authors reported medication changes based on CAC scores. Finally, there was no comparative assessment of other primary prevention CVD testing—such as lipids, inflammatory markers, or stress testing—that could have an impact on not only CVD but also all-cause event rates.

The data the authors present corroborate previous reports demonstrating a relative benefit of CAC scoring compared with other modalities of CVD testing such as cholesterol and inflammatory markers. Certainly, those tested surrogate markers are just risk factors for coronary artery disease and not the disease itself. Controlling for risk factors does not always lower the risk of disease, because most patients have relatively normal laboratory numbers and risk factors when they present for the first cardiovascular event.^4,5 Recall that Rumberger and Kaufman⁶ demonstrated that coronary calcium is only 20% of the total plaque volume—a figurative tip of the atherosclerotic iceberg. Therefore, the detection of coronary calcium would suggest that there has been an evolution and progression of atherosclerotic coronary disease over many years and there are many plaques in different phases of maturation that could put the patient at risk. Indeed, coronary calcification can reclassify up to two-thirds of patients into higher risk scores over vascular reactivity testing, ankle-brachial index testing, inflammatory markers such as C-reactive protein, and family history of coronary artery disease.⁶ Furthermore, a negative coronary calcium score of 0, per the Multi-Ethnic Study of Atherosclerosis study, would indicate that the patient could have a 4- to 5-year relatively event-free rate.⁷

Despite the positive data on CAC testing, it still begs the question regarding the direct impact of testing on outcomes. Moreover, the downstream ramifications of testing that could originate from this initial screening were not described in this paper. It is not always biologically plausible to infer that simply undergoing a test will improve outcomes. First, these data demonstrate that patients with physicians who order screening tests likely have better insurance, socioeconomic status, inclination toward positive diet/exercise habits, and overall health care to deliver a reduction in events. Second, it is possible that the results from the CAC tests performed the intended function to guide primary prevention care in the form of healthier lifestyle habits, improved medication profile and adherence, and resultant improved outcomes. As mentioned previously, this large cohort of patients could have the statistical power to demonstrate an outcome benefit with statins for primary prevention.³ Indeed, further elucidation of the mechanisms behind these findings is warranted with the hope of potentially providing some primary prevention benefit to patients who may or may not be aware of their underlying CVD risk.

Thus, CAC testing may provide a benefit in terms of outcomes and all-cause mortality when applied to a fairly young and engaged population with hyperlipidemia. The field will need additional work to understand the mechanism behind this benefit to identify the specific patient population for which routine CAC scoring should be obtained for maximum benefit. Leveraging these large, multicenter, diverse populations could provide the necessary information to produce a primary prevention screening tool that can maximize outcomes.

—R. Jay Widmer, MD, PhD 
Baylor Scott & White Medical Center – Temple
Temple, Texas
Robert.Widmer@bswhealth.org http://orcid.org/0000-0002-3063-5651