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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

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@article{34bcd254bb4947cd82526f4bf96671cf,
title = "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",
abstract = "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.",
author = "Erik Nilsson and Jens Kastrup and Ahmad Sajadieh and {Boje Jensen}, Gorm and Erik Kj{\o}ller and Kolmos, {Hans J{\o}rn} and Jonas Wuopio and Christoph Nowak and Anders Larsson and Jakobsen, {Janus Christian} and Per Winkel and Christian Gluud and Iversen, {Kasper K} and Johan {\"A}rnl{\"o}v and Carlsson, {Axel C}",
year = "2020",
month = "1",
day = "18",
doi = "10.3390/jcm9010265",
language = "English",
volume = "9",
journal = "Journal of Clinical Medicine",
issn = "2077-0383",
publisher = "M D P I AG",
number = "1",

}

RIS

TY - JOUR

T1 - 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

AU - Nilsson, Erik

AU - Kastrup, Jens

AU - Sajadieh, Ahmad

AU - Boje Jensen, Gorm

AU - Kjøller, Erik

AU - Kolmos, Hans Jørn

AU - Wuopio, Jonas

AU - Nowak, Christoph

AU - Larsson, Anders

AU - Jakobsen, Janus Christian

AU - Winkel, Per

AU - Gluud, Christian

AU - Iversen, Kasper K

AU - Ärnlöv, Johan

AU - Carlsson, Axel C

PY - 2020/1/18

Y1 - 2020/1/18

N2 - 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.

AB - 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.

U2 - 10.3390/jcm9010265

DO - 10.3390/jcm9010265

M3 - Journal article

VL - 9

JO - Journal of Clinical Medicine

JF - Journal of Clinical Medicine

SN - 2077-0383

IS - 1

ER -

ID: 59121220