Nonobstructive Coronary Plaque Detected by CT Predicts Mortality

Abstract & Commentary

By Andrew J. Boyle, MBBS, PhD, Assistant Professor of Medicine, Interventional Cardiology, University of California, San Francisco. Dr. Boyle reports no financial relationship relevant to this field of study.

Source: Lin FY, et al. Mortality risk in symptomatic patients with nonobstructive coronary artery disease. J Am Coll Cardiol 2011;58:510-519.

Computed tomography (CT) imaging has progressed substantially in recent years, and we are now able to non-invasively image coronary artery disease in many patients. While we have copious data on outcomes of patients with obstructive coronary artery disease, little is known about the outcomes in patients who have non-obstructive coronary artery plaque. In part, this is due to the fact that we were previously unable to image the coronary arteries without invasive coronary angiography, which carries some inherent risk. Therefore, only patients with significant symptoms and/or signs of obstructive coronary artery disease, such as a positive stress test, are usually subjected to invasive angiography. In addition, invasive coronary angiography does not image the wall of the coronary artery, only the lumen, and may miss nonobstructive coronary plaque. Lin and colleagues studied the outcomes of patients with nonobstructive plaque detected by CT coronary angiography (CTCA).

In a two-center study, 2583 consecutive patients undergoing CTCA were studied for the primary endpoint of mortality. Indications for the CTCA were chest pain in 85% and others (peripheral arterial disease, cerebrovascular disease, screening) in 15%. They excluded all patients with prior known coronary artery disease (CAD), including prior revascularization, and those with any lesions (defined as ≥ 50% stenosis). Social security death index was searched to determine all-cause mortality. They censored early death (within 90 days of CTCA) to exclude deaths attributable to acute coronary syndromes.

Over a median of 3.1 ± 0.5 years follow-up, total mortality was 2.3%. The average age was 53 ± 14 years and 42% were male, 15% had diabetes, 51% dyslipidemia, and 28% were smokers. Patients with no identifiable coronary plaque had low mortality (1.2% overall; annualized mortality 0.34%). A higher burden of plaque was associated with age, male gender, hypertension, diabetes, dyslipidemia, and past smoking. After adjustment for traditional coronary risk factors, the presence of nonobstructive plaque was associated with higher mortality. The presence of any plaque was associated with an adjusted hazard ratio of 1.98 compared to no plaque (P < 0.05). Furthermore, a greater extent of plaque was associated with even greater mortality. Patients with nonobstructive plaque in three epicardial vessels had an adjusted hazard ratio of 4.75 compared to no plaque (P < 0.001), and those with ≥ 5 segments affected had an adjusted hazard ratio of 5.12 compared to no plaque (P < 0.001). As a validation, they showed in their cohort that mortality was associated with age, diabetes, dyslipidemia, and smoking.

Even in patients who are not considered to be at high risk (Framingham estimated 10-year risk < 10%), the presence of plaque was associated with higher mortality (3.4%; P < 0.001 vs no plaque). In patients who had no treatable risk factors (diabetes, dyslipidemia, hypertension), the presence of plaque was still associated with a higher mortality (6.7%; P < 0.001 vs no plaque). Compared to Framingham risk, the presence of any plaque showed an improved net reclassification improvement (20.5%; P = 0.04). Interestingly, despite the strong association between plaque burden and mortality, there was no association between plaque composition and mortality in this cohort. The authors conclude that the presence and extent of nonobstructive plaques augment prediction of incident mortality beyond conventional clinical risk assessment.

Commentary

This is a very provocative study showing a doubling of mortality with the presence of any plaque on CTCA, and a 5-fold increase in mortality for widespread nonobstructive plaque, despite correcting for traditional risk factors. Furthermore, even patients at low clinical risk and without treatable traditional risk factors had increased mortality in the presence of nonobstructive coronary plaque. This suggests that there may be a significant gap in our current assessment and management of CAD — there are patients we are not identifying with clinical risk prediction who remain at high risk and are currently not captured by treatment guidelines. However, as with any new diagnostic test, we still do not know if treatment based on these findings will alter the clinical outcomes, and if so, whether it is cost effective to test and treat in this way. As this field evolves, carefully designed prospective clinical trials are needed to test this approach.

There are several limitations of this study that should be mentioned. First, the treatment of patients was at the discretion of the physician. Because the results of the study were disclosed, they may have altered treatment decisions and this is therefore, not truly a natural history study. Furthermore, we are not told of the treatment regimens of patients, in particular how well their lipids and blood pressure were controlled, and whether any changes based on the test results altered outcomes. Second, all-cause mortality as the primary endpoint does not necessarily define a cause and effect relationship between coronary plaque and death. There are many possible unmeasured confounders in this patient cohort and, thus, the results should be interpreted with caution. Third, this cohort was predominantly a chest-pain cohort with a minority undergoing CTCA for non-chest pain indications. Therefore, the results cannot be generalized to the community at large and one cannot recommend screening for CAD in asymptomatic patients based on the results of this study. These results, while compelling in their magnitude, should be considered hypothesis-generating only. As CTCA technology continues to evolve, and radiation doses are becoming lower with more widespread use of prospective gating, it is likely that noninvasive imaging of coronary plaque will find some place in our assessment and management of CAD. However, at this time, the precise use of CTCA remains to be more fully defined.