Background: 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.

Methods: 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.

Results: 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%]; P<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%; P<0.001). In contrast, any abnormality on FT was significantly more specific for predicting events (78.6% for FT versus 35.2% for CAC; P<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).

Conclusions: 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.

Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01174550.

背景：冠状动脉钙（CAC）是无症状患者未来重大不良动脉粥样硬化性心血管事件的既定预测因素。但是，关于在评估有症状患者的预后方面，如何将CAC与功能测试（FT）进行比较的数据有限。

方法：在PROMISE试验（用于评估胸痛的前瞻性多中心影像学研究）中，患有稳定胸痛（或呼吸困难）且阻塞性冠状动脉疾病的中等预测可能性的患者被随机分配至FT（运动心电图，核应力或应力超声心动图）或解剖学测试。我们评估了那些接受了CAC测试的患者，作为解剖学评估的一部分（n = 4209），并将其与FT的结果（n = 4602）进行了比较。我们将CAC和FT结果分为正常或轻度，中度或严重异常（对于CAC：0，1–99 Agatston评分[AS]，100–400 AS和> 400 AS；对于FT：正常，轻度=晚期跑步机，中度=早期跑步机或单支血管缺血，重度=大局部缺血区域异常）。主要终点是全因死亡，心肌梗死，中位随访26.1个月或不稳定型心绞痛住院治疗。使用Cox回归模型计算危险比（HRs）和C统计量，以确定预测值和歧视值。

结果：总体而言，正常和轻度，中度或重度异常测试结果的分布在FT和CAC之间有显着差异（FT：正常，n = 3588 [78.0％]；轻度，n = 432 [9.4％]；中度，n = 432）。 n = 217 [4.7％]；严重，n = 365 [7.9％]； CAC：正常，n = 1457 [34.6％]；轻度，n = 1340 [31.8％]；中度，n = 772 [18.3％]；严重，n = 640 [15.2％]；P<0.0001）。两组的中度和严重异常均能强有力地预测事件（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；严重：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（n = 112/133，占84％）发生在CAC检测呈阳性（评分> 0）的患者中，而少于一半的事件发生在轻度，中度或严重异常患者中FT（n ＝ 132，为57，43％；P＜0.001）。相比之下，FT的任何异常对预测事件的特异性都更高（FT的78.6％与CAC的35.2％；P<0.001）。预测死亡率，非致命性心肌梗塞和不稳定型心绞痛住院的主要终点的总体区分能力对于CAC和FT都是相似且公平的（C统计，0.67比0.64）。与FT和CAC检测相比，冠状动脉计算机断层血管造影可提供更好的预后信息（C指数，0.72）。

结论：在稳定的可疑冠心病患者中，大多数发生临床事件的患者在基线时可测量的CAC，只有不到一半的患者出现FT异常。但是，异常的FT对心血管事件更具特异性，导致这两种测试的总体鉴别能力相似。

临床试验注册： URL：https : //www.clinicaltrials.gov。唯一标识符：NCT01174550。