Budoff Matthew J, Mayrhofer Thomas, Ferencik Maros, Bittner Daniel, Lee Kerry L, Lu Michael T, Coles Adrian, Jang James, Krishnam Mayil, Douglas Pamela S, Hoffmann Udo
Los Angeles Biomedical Research Institute, Torrance, CA (M.J.B.)
Cardiac MR PET CT Program, Massachusetts General Hospital, Harvard Medical School, Boston (T.M., M.F., D.B., M.T.L., U.H.).
Circulation. 2017 Nov 21;136(21):1993-2005. doi: 10.1161/CIRCULATIONAHA.117.030578. Epub 2017 Aug 28.
Coronary artery calcium (CAC) is an established predictor of future major adverse atherosclerotic cardiovascular events in asymptomatic individuals. However, limited data exist as to how CAC compares with functional testing (FT) in estimating prognosis in symptomatic patients.
In the PROMISE trial (Prospective Multicenter Imaging Study for Evaluation of Chest Pain), patients with stable chest pain (or dyspnea) and intermediate pretest probability for obstructive coronary artery disease were randomized to FT (exercise electrocardiography, nuclear stress, or stress echocardiography) or anatomic testing. We evaluated those who underwent CAC testing as part of the anatomic evaluation (n=4209) and compared that with results of FT (n=4602). We stratified CAC and FT results as normal or mildly, moderately, or severely abnormal (for CAC: 0, 1-99 Agatston score [AS], 100-400 AS, and >400 AS, respectively; for FT: normal, mild=late positive treadmill, moderate=early positive treadmill or single-vessel ischemia, and severe=large ischemic region abnormality). The primary end point was all-cause death, myocardial infarction, or unstable angina hospitalization over a median follow-up of 26.1 months. Cox regression models were used to calculate hazard ratios (HRs) and C statistics to determine predictive and discriminatory values.
Overall, the distribution of normal or mildly, moderately, or severely abnormal test results was significantly different between FT and CAC (FT: normal, n=3588 [78.0%]; mild, n=432 [9.4%]; moderate, n=217 [4.7%]; severe, n=365 [7.9%]; CAC: normal, n=1457 [34.6%]; mild, n=1340 [31.8%]; moderate, n=772 [18.3%]; severe, n=640 [15.2%]; <0.0001). Moderate and severe abnormalities in both arms robustly predicted events (moderate: CAC: HR, 3.14; 95% confidence interval, 1.81-5.44; and FT: HR, 2.65; 95% confidence interval, 1.46-4.83; severe: CAC: HR, 3.56; 95% confidence interval, 1.99-6.36; and FT: HR, 3.88; 95% confidence interval, 2.58-5.85). In the CAC arm, the majority of events (n=112 of 133, 84%) occurred in patients with any positive CAC test (score >0), whereas fewer than half of events occurred in patients with mildly, moderately, or severely abnormal FT (n=57 of 132, 43%; <0.001). In contrast, any abnormality on FT was significantly more specific for predicting events (78.6% for FT versus 35.2% for CAC; <0.001). Overall discriminatory ability in predicting the primary end point of mortality, nonfatal myocardial infarction, and unstable angina hospitalization was similar and fair for both CAC and FT (C statistic, 0.67 versus 0.64). Coronary computed tomographic angiography provided significantly better prognostic information compared with FT and CAC testing (C index, 0.72).
Among stable outpatients presenting with suspected coronary artery disease, most patients experiencing clinical events have measurable CAC at baseline, and fewer than half have any abnormalities on FT. However, an abnormal FT was more specific for cardiovascular events, leading to overall similarly modest discriminatory abilities of both tests.
URL: https://www.clinicaltrials.gov. Unique identifier: NCT01174550.
冠状动脉钙化（CAC）是无症状个体未来发生主要不良动脉粥样硬化性心血管事件的既定预测指标。然而，关于在有症状患者中CAC与功能测试（FT）在评估预后方面的比较，现有数据有限。
在PROMISE试验（前瞻性多中心胸痛评估影像研究）中，有稳定胸痛（或呼吸困难）且阻塞性冠状动脉疾病预检概率为中等的患者被随机分配接受FT（运动心电图、核素负荷试验或负荷超声心动图）或解剖学检查。我们评估了作为解剖学评估一部分接受CAC检测的患者（n = 4209），并将其与FT结果（n = 4602）进行比较。我们将CAC和FT结果分层为正常或轻度、中度或重度异常（对于CAC：分别为0、1 - 99阿加斯顿评分[AS]、100 - 400 AS和>400 AS；对于FT：正常、轻度 = 平板运动晚期阳性、中度 = 平板运动早期阳性或单支血管缺血、重度 = 大面积缺血区域异常）。主要终点是在中位随访26.1个月期间的全因死亡、心肌梗死或不稳定型心绞痛住院。使用Cox回归模型计算风险比（HRs）和C统计量以确定预测和鉴别价值。
总体而言，FT和CAC之间正常或轻度、中度或重度异常检测结果的分布存在显著差异（FT：正常，n = 3588 [78.0%]；轻度，n = 432 [9.4%]；中度，n = 217 [4.7%]；重度，n = 365 [7.9%]；CAC：正常，n = 1457 [34.6%]；轻度，n = 1340 [31.8%]；中度，n = 772 [18.3%]；重度，n = 640 [15.2%]；<0.0001）。两组中的中度和重度异常均有力地预测了事件（中度：CAC：HR，3.14；95%置信区间，1.81 - 5.44；FT：HR，2.65；95%置信区间，1.46 - 4.83；重度：CAC：HR，3.56；95%置信区间，1.99 - 6.36；FT：HR，3.88；95%置信区间，2.58 - 5.85）。在CAC组中，大多数事件（133例中的112例，84%）发生在任何CAC检测呈阳性（评分>0）的患者中，而在FT轻度、中度或重度异常的患者中发生的事件不到一半（132例中的57例，43%；<0.001）。相比之下，FT上的任何异常在预测事件方面具有显著更高的特异性（FT为78.6%，CAC为35.2%；<0.001）。在预测死亡率、非致命性心肌梗死和不稳定型心绞痛住院的主要终点方面，总体鉴别能力对CAC和FT而言相似且一般（C统计量，0.67对0.64）。与FT和CAC检测相比，冠状动脉计算机断层血管造影提供了显著更好的预后信息（C指数，0.72）。
在疑似冠状动脉疾病的稳定门诊患者中，大多数发生临床事件的患者在基线时有可测量的CAC，且不到一半的患者FT有任何异常。然而，FT异常对心血管事件更具特异性，导致两种检测的总体鉴别能力同样一般。
