TY - JOUR
T1 - Impact of C-reactive protein levels on lipoprotein(a)-associated aortic stenosis incidence and progression
AU - Girard, Arnaud
AU - Gaillard, Emilie
AU - Puri, Rishi
AU - Capoulade, Romain
AU - Chan, Kwan L.
AU - Paulin, Audrey
AU - Manikpurage, Hasanga D.
AU - Dumesnil, Jean
AU - Tam, James W.
AU - Teo, Koon K.
AU - Couture, Christian
AU - Wareham, Nicholas J.
AU - Clavel, Marie-Annick
AU - Stroes, Erik S. G.
AU - Mathieu, Patrick
AU - Thériault, S. bastien
AU - Tsimikas, Sotirios
AU - Pibarot, Philippe
AU - Boekholdt, S. Matthijs
AU - Arsenault, Benoit J.
N1 - Funding Information: B.J.A. holds a senior scholar award from the Fonds de recherche du Québec: Santé and is supported by grants from the Canadian Institutes of Health Research and the Foundation of the Quebec Heart and Lung Institute. P.M. is the recipient of the Joseph C. Edwards Foundation granted to Université Laval. R.C. is supported by a 'Connect Talent' research chair from Region Pays de la Loire and Nantes Métropole. M.-A.C. holds the Canada Research Chair on Women's Cardiac Valvular Health. Funding Information: B.J.A. holds a senior scholar award from the Fonds de recherche du Québec: Santé and is supported by grants from the Canadian Institutes of Health Research and the Foundation of the Quebec Heart and Lung Institute. P.M. is the recipient of the Joseph C. Edwards Foundation granted to Université Laval. R.C. is supported by a ‘Connect Talent’ research chair from Region Pays de la Loire and Nantes Métropole. M.-A.C. holds the Canada Research Chair on Women’s Cardiac Valvular Health. Funding Information: Conflict of interest: B.J.A. is a consultant for Novartis, Editas Medicine, and Silence Therapeutics and has received research contracts from Pfizer, Ionis Pharmaceuticals, and Silence Therapeutics. R.C. has received honorarium from Novartis. P.P. has received funding from Edwards Lifesciences, Medtronic, Pi-Cardia, and Cardiac Phoenix for echocardiography core laboratory analyses and research studies in the field of transcatheter valve therapies, for which he received no personal compensation. P.P. has received lecture fees from Edwards Lifesciences and Medtronic. S.T. is a coinventor of monoclonal antibodies directed to Lp(a) owned by UCSD directed to Lp(a) and receives royalties from patents on oxidation-specific antibodies and of biomarkers related to oxidised lipoproteins and Lp(a) held by UCSD. S.T. is a cofounder and have an equity interest in Oxitope, Inc. and its affiliates (‘Oxitope’) as well as in Kleanthi Diagnostics, LLC (‘Kleanthi’). The terms of this arrangement have been reviewed and approved by the UCSD, in accordance with its conflict-of-interest policies. S.T. has a dual appointment at University of California San Diego and Ionis Pharmaceuticals. Publisher Copyright: © 2023 The Author(s).
PY - 2023/3/1
Y1 - 2023/3/1
N2 - 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.
AB - 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.
KW - C-reactive protein
KW - Calcific aortic valve stenosis
KW - Lipoprotein(a)
UR - http://www.scopus.com/inward/record.url?scp=85163148081&partnerID=8YFLogxK
U2 - https://doi.org/10.1093/ehjopen/oead032
DO - https://doi.org/10.1093/ehjopen/oead032
M3 - Article
C2 - 37077580
SN - 2752-4191
VL - 3
JO - European heart journal open
JF - European heart journal open
IS - 2
M1 - oead032
ER -