Impact of C-reactive protein levels on lipoprotein(a)-associated aortic stenosis incidence and progression

European Heart Journal Open · 20 authors, 25 centres

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TL;DR

Two large prospective cohorts, EPIC-Norfolk and the UK Biobank, were used to assess CAVS incidence.

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Two large prospective cohorts, EPIC-Norfolk and the UK Biobank, were used to assess CAVS incidence. A third study, ASTRONOMER, evaluated the progression of pre-existing aortic stenosis. A similar predictive pattern for Lp(a) was seen in the UK Biobank. In the ASTRONOMER study, the progression of aortic stenosis was comparable in patients with elevated Lp(a) regardless of CRP status. Limitations include the post-hoc nature of the ASTRONOMER analysis, the reliance on electronic health records for CAVS diagnosis in the cohorts, and the lack of information on aortic valve phenotypes.

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cohort

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cardiology

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ORIGINAL PAPER

PMC10108885

Impact of C-reactive protein levels on lipoprotein(a)-associated aortic stenosis incidence and progression

European Heart Journal Open

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ABSTRACT

Abstract Aims Elevated lipoprotein(a) [Lp(a)] levels are associated with the risk of coronary artery disease (CAD) and calcific aortic valve stenosis (CAVS). Observational studies revealed that Lp(a) and C-reactive protein (CRP) levels, a biomarker of systemic inflammation, may jointly predict CAD risk. Whether Lp(a) and CRP levels also jointly predict CAVS incidence and progression is unknown. Methods and results We investigated the association of Lp(a) with CAVS according to CRP levels in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk study ( n = 18 226, 406 incident cases) and the UK Biobank ( n = 438 260, 4582 incident cases), as well as in the ASTRONOMER study ( n = 220), which assessed the haemodynamic progression rate of pre-existing mild-to-moderate aortic stenosis. In EPIC-Norfolk, in comparison to individuals with low Lp(a) levels (<50 mg/dL) and low CRP levels (<2.0 mg/L), those with elevated Lp(a) (>50 mg/dL) and low CRP levels (<2.0 mg/L) and those with elevated Lp(a) (>50 mg/dL) and elevated CRP levels (>2.0 mg/L) had a higher CAVS risk [hazard ratio (HR) = 1.86 (95% confidence intervals, 1.30–2.67) and 2.08 (1.44–2.99), respectively]. A comparable predictive value of Lp(a) in patients with vs. without elevated CRP levels was also noted in the UK Biobank. In ASTRONOMER, CAVS progression was comparable in patients with elevated Lp(a) levels with or without elevated CRP levels. Conclusion Lp(a) predicts the incidence and possibly progression of CAVS regardless of plasma CRP levels. Lowering Lp(a) levels may warrant further investigation in the prevention and treatment of CAVS, regardless of systemic inflammation. Keywords: Calcific aortic valve stenosis, Lipoprotein(a), C-reactive protein

CITATION EXPORT

Arnaud Girard, Emilie Gaillard, Rishi Puri et al.. Impact of C-reactive protein levels on lipoprotein(a)-associated aortic stenosis incidence and progression. European Heart Journal Open. (2023). https://doi.org/10.1093/ehjopen/oead032

AUTHORS

20 · 25 CENTRES

Arnaud Girard, Emilie Gaillard, Rishi Puri, Romain Capoulade, Kwan L Chan, Audrey Paulin, Hasanga D Manikpurage, Jean Dumesnil, James W Tam, Koon K Teo, Christian Couture, Nicholas J Wareham, Marie-Annick Clavel, Erik S G Stroes, Patrick Mathieu, Sébastien Thériault, Sotirios Tsimikas, Philippe Pibarot, S Matthijs Boekholdt, Benoit J Arsenault

1 Centre de recherche de l’Institut universitaire de cardiologie et de pneumologie de Québec, Québec, QC, G1V 4G5, Canada
2 Department of Cardiology, Amsterdam UMC, University of Amsterdam, Amsterdam, 1105 AZ, The Netherlands
3 Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, OH, 44195, USA
4 Nantes Université, CNRS, INSERM, l’institut du thorax, F-44000 Nantes, 44007, France
5 Department of Medicine, University of Ottawa Heart Institute, Ottawa, ON, K1Y 4W7, Canada
6 Centre de recherche de l’Institut universitaire de cardiologie et de pneumologie de Québec, Québec, QC, G1V 4G5, Canada
7 Centre de recherche de l’Institut universitaire de cardiologie et de pneumologie de Québec, Québec, QC, G1V 4G5, Canada
8 Centre de recherche de l’Institut universitaire de cardiologie et de pneumologie de Québec, Québec, QC, G1V 4G5, Canada
9 Department of Medicine, St. Boniface General Hospital, Winnipeg, MB, R2H 2A6, Canada
10 Department of Medicine (Cardiology), McMaster University, Hamilton, ON, L8S 4L8, Canada
11 Centre de recherche de l’Institut universitaire de cardiologie et de pneumologie de Québec, Québec, QC, G1V 4G5, Canada
12 Department of Public Health and Primary Care, University of Cambridge, Cambridge, CB2 1TN, UK
13 Centre de recherche de l’Institut universitaire de cardiologie et de pneumologie de Québec, Québec, QC, G1V 4G5, Canada
14 Department of Medicine, Faculty of Medicine, Université Laval, Québec, QC, G1V 0A6, Canada
15 Department of Vascular Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, 1105 AZ, The Netherlands
16 Centre de recherche de l’Institut universitaire de cardiologie et de pneumologie de Québec, Québec, QC, G1V 4G5, Canada
17 Department of Surgery, Faculty of Medicine, Université Laval, Québec, QC, G1V 0A6, Canada
18 Centre de recherche de l’Institut universitaire de cardiologie et de pneumologie de Québec, Québec, QC, G1V 4G5, Canada
19 Department of Molecular Biology, Medical Biochemistry and Pathology, Faculty of Medicine, Université Laval, Québec, QC, G1V 0A6, Canada
20 Division of Cardiovascular Diseases, Department of Medicine, University of California San Diego, La Jolla, CA, 92093, USA
21 Centre de recherche de l’Institut universitaire de cardiologie et de pneumologie de Québec, Québec, QC, G1V 4G5, Canada
22 Department of Medicine, Faculty of Medicine, Université Laval, Québec, QC, G1V 0A6, Canada
23 Department of Cardiology, Amsterdam UMC, University of Amsterdam, Amsterdam, 1105 AZ, The Netherlands
24 Centre de recherche de l’Institut universitaire de cardiologie et de pneumologie de Québec, Québec, QC, G1V 4G5, Canada
25 Department of Medicine, Faculty of Medicine, Université Laval, Québec, QC, G1V 0A6, Canada