Pregnancy Associated Plasma Protein-A as a Cardiovascular Risk Marker in Patients with Stable Coronary Heart Disease During 10 Years Follow-Up-A CLARICOR Trial Sub-Study

Erik Nilsson*, Jens Kastrup, Ahmad Sajadieh, Gorm Boje Jensen, Erik Kjoller, Hans Jorn Kolmos, Jonas Wuopio, Christoph Nowak, Anders Larsson, Janus Christian Jakobsen, Per Winkel, Christian Gluud, Kasper K. Iversen, Johan Arnlov, Axel C. Carlsson

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Abstrakt

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 (n = 1.996) and the clarithromycin group the replication cohort (n = 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, 95CI) 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, 95.24-1.70; replication HR 1.29, 95.10-1.52). 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.
OriginalsprogEngelsk
Artikelnummer265
TidsskriftJournal of Clinical Medicine
Vol/bind9
Udgave nummer1
Antal sider11
ISSN2077-0383
DOI
StatusUdgivet - 18. jan. 2020

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