Age- and Sex-Related Differences in All-Cause Mortality Risk Based on Coronary Computed Tomography Angiography Findings: Results From the International Multicenter CONFIRM (Coronary CT Angiography Evaluation for Clinical Outcomes: An International Multicenter Registry) of 23,854 Patients Without Known Coronary Artery Disease

Study Questions:

What is the predictive value of nonobstructive and obstructive coronary artery disease (CAD) as assessed by ≥64-detector row coronary computed tomography angiography (CCTA) for intermediate-term mortality risk stratified by age and sex?

Methods:

The investigators evaluated a consecutive cohort of 24,775 patients undergoing ≥64-detector row CCTA between 2005 and 2009 without known CAD who met inclusion criteria. In these patients, CAD by CCTA was defined as none (0% stenosis), mild (1-49% stenosis), moderate (50-69% stenosis), or severe (≥70% stenosis). CAD severity was judged on a per-patient, per-vessel, and per-segment basis. Time to mortality was estimated using multivariable Cox proportional hazards models.

Results:

At a 2.3 ± 1.1-year follow-up, 404 deaths had occurred. In risk-adjusted analysis, both per-patient obstructive (hazard ratio [HR], 2.60; 95% confidence interval [CI], 1.94-3.49; p < 0.0001) and nonobstructive (HR, 1.60; 95% CI, 1.18-2.16; p = 0.002) CAD conferred increased risk of mortality compared with patients without evident CAD. Incident mortality was associated with a dose-response relationship to the number of coronary vessels exhibiting obstructive CAD, with increasing risk observed for nonobstructive (HR, 1.62; 95% CI, 1.20-2.19; p = 0.002), obstructive one-vessel (HR, 2.00; 95% CI, 1.43-2.82; p < 0.0001), two-vessel (HR, 2.92; 95% CI, 2.00-4.25; p < 0.0001), or three-vessel or left main (HR, 3.70; 95% CI, 2.58-5.29; p < 0.0001) CAD. Importantly, the absence of CAD by CCTA was associated with a low rate of incident death (annualized death rate: 0.28%). When stratified by age <65 years versus ≥65 years, younger patients experienced higher hazards for death for two-vessel (HR, 4.00; 95% CI, 2.16-7.40; p < 0.0001 vs. HR, 2.46; 95% CI, 1.51-4.02; p = 0.0003) and three-vessel (HR, 6.19; 95% CI, 3.43-11.2; p < 0.0001 vs. HR, 3.10; 95% CI, 1.95-4.92; p < 0.0001) CAD. The relative hazard for three-vessel CAD (HR, 4.21; 95% CI, 2.47-7.18; p < 0.0001 vs. HR, 3.27; 95% CI, 1.96-5.45; p < 0.0001) was higher for women as compared with men.

Conclusions:

The authors concluded that nonobstructive and obstructive CAD by CCTA is associated with higher rates of mortality, with risk profiles differing for age and sex.

Perspective:

This prospective, multicenter registry suggests that extent and severity of CAD by CCTA successfully identifies individuals at heightened risk for all-cause mortality. The presence of both obstructive and nonobstructive CAD by CCTA on a per-patient, per-vessel, and per-segment basis portends worsened prognosis, with differential risk noted between sex and age groups. There is prognostic value for nonobstructive CAD detection and one-vessel obstructive CAD in women, but not in men. It is possible that the identification of nonobstructive disease in women led clinicians to pursue alternative noncardiac diagnoses for symptoms, and lack of aggressive treatment for these CAD findings resulted in heightened risk of incident death, but this hypothesis needs further study.

Keywords: Prognosis, Coronary Artery Disease, Follow-Up Studies, Coronary Angiography, Tomography, Cardiology


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