Nilsson Erik, Kastrup Jens, Sajadieh Ahmad, Boje Jensen Gorm, Kjøller Erik, Kolmos Hans Jørn, Wuopio Jonas, Nowak Christoph, Larsson Anders, Jakobsen Janus Christian, Winkel Per, Gluud Christian, Iversen Kasper K, Ärnlöv Johan, Carlsson Axel C
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, 17177 Stockholm, Sweden.
School of Medical Sciences, Örebro University, 70182 Örebro, Sweden.
J Clin Med. 2020 Jan 18;9(1):265. doi: 10.3390/jcm9010265.
Elevated pregnancy-associated plasma protein A (PAPP-A) is associated with mortality in acute coronary syndromes. Few studies have assessed PAPP-A in stable coronary artery disease (CAD) and results are conflicting. We assessed the 10-year prognostic relevance of PAPP-A levels in stable CAD. The CLARICOR trial was a randomized controlled clinical trial including outpatients with stable CAD, randomized to clarithromycin versus placebo. The placebo group constituted our discovery cohort ( = 1.996) and the clarithromycin group the replication cohort ( = 1.975). The composite primary outcome was first occurrence of cardiovascular event or death. In the discovery cohort, incidence rates (IR) for the composite outcome were higher in those with elevated PAPP-A (IR 12.72, 95% Confidence Interval (CI) 11.0-14.7 events/100 years) compared to lower PAPP-A (IR 8.78, 8.25-9.34), with comparable results in the replication cohort. Elevated PAPP-A was associated with increased risk of the composite outcome in both cohorts (discovery Hazard Ratio (HR) 1.45, 95% CI 1.24-1.70; replication HR 1.29, 95% CI 1.10-1.52). In models adjusted for established risk factors, these trends were attenuated. Elevated PAPP-A was associated with higher all-cause mortality in both cohorts. We conclude that elevated PAPP-A levels are associated with increased long-term mortality in stable CAD, but do not improve long-term prediction of death or cardiovascular events when added to established predictors.
妊娠相关血浆蛋白A（PAPP-A）升高与急性冠脉综合征的死亡率相关。很少有研究评估稳定型冠状动脉疾病（CAD）中的PAPP-A，且结果相互矛盾。我们评估了稳定型CAD中PAPP-A水平与10年预后的相关性。CLARICOR试验是一项随机对照临床试验，纳入稳定型CAD门诊患者，随机分为克拉霉素组和安慰剂组。安慰剂组构成我们的发现队列（n = 1996），克拉霉素组构成重复队列（n = 1975）。复合主要结局是首次发生心血管事件或死亡。在发现队列中，PAPP-A升高者的复合结局发生率（IR）高于PAPP-A较低者（IR 12.72，95%置信区间（CI）11.0-14.7事件/100年）（IR 8.78，8.25-9.34），重复队列结果类似。两个队列中，PAPP-A升高均与复合结局风险增加相关（发现队列风险比（HR）1.45，95%CI 1.24-1.70；重复队列HR 1.29，95%CI 1.10-1.52）。在针对既定危险因素进行调整的模型中，这些趋势有所减弱。两个队列中，PAPP-A升高均与全因死亡率较高相关。我们得出结论，稳定型CAD中PAPP-A水平升高与长期死亡率增加相关，但在既定预测指标基础上加入PAPP-A并不能改善死亡或心血管事件的长期预测。
