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Open AccessArticle

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

1
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, 17177 Stockholm, Sweden
2
School of Medical Sciences, Örebro University, 70182 Örebro, Sweden
3
Department of Cardiology, Rigshospitalet University of Copenhagen, 2100 Copenhagen, Denmark
4
Department of Cardiology, Copenhagen University Hospital of Bispebjerg and Frederiksberg, 2000 Frederiksberg, Denmark
5
Department of Cardiology, Hvidovre Hospital University of Copenhagen, 2650 Hvidovre, Denmark
6
Department of Cardiology S, Herlev Hospital University of Copenhagen, 2730 Herlev, Denmark
7
Department of Clinical Microbiology, Odense University Hospital, 5000 Odense, Denmark
8
Department of Medicine, Mora County Hospital, 79251 Mora, Sweden
9
Division for Family Medicine and Primary Care, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, 14183 Huddinge, Sweden
10
Department of Medical Sciences, Uppsala University, 75185 Uppsala, Sweden
11
Copenhagen Trial Unit, Centre for Clinical Intervention Research, Rigshospitalet, Copenhagen University Hospital, 2100 Copenhagen, Denmark
12
Department of Cardiology, Holbæk Hospital, 4300 Holbæk, Denmark
13
School of Health and Social Studies, Dalarna University, 79131 Falun, Sweden
*
Author to whom correspondence should be addressed.
J. Clin. Med. 2020, 9(1), 265; https://doi.org/10.3390/jcm9010265
Received: 5 December 2019 / Revised: 11 January 2020 / Accepted: 15 January 2020 / Published: 18 January 2020
(This article belongs to the Special Issue Novel Biomarkers for Heart Disease)
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, 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. View Full-Text
Keywords: pregnancy-associated plasma protein-A; coronary artery disease; cohort studies; biomarkers pregnancy-associated plasma protein-A; coronary artery disease; cohort studies; biomarkers
MDPI and ACS Style

Nilsson, E.; Kastrup, J.; Sajadieh, A.; Boje Jensen, G.; Kjøller, E.; Kolmos, H.J.; Wuopio, J.; Nowak, C.; Larsson, A.; Jakobsen, J.C.; Winkel, P.; Gluud, C.; Iversen, K.K; Ärnlöv, J.; Carlsson, A.C. 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. J. Clin. Med. 2020, 9, 265. https://doi.org/10.3390/jcm9010265

AMA Style

Nilsson E, Kastrup J, Sajadieh A, Boje Jensen G, Kjøller E, Kolmos HJ, Wuopio J, Nowak C, Larsson A, Jakobsen JC, Winkel P, Gluud C, Iversen KK, Ärnlöv J, Carlsson AC. 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. Journal of Clinical Medicine. 2020; 9(1):265. https://doi.org/10.3390/jcm9010265

Chicago/Turabian Style

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. 2020. "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" J. Clin. Med. 9, no. 1: 265. https://doi.org/10.3390/jcm9010265

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