Lipoprotein-associated phospholipase A2 activity, genetics and calcific aortic valve stenosis in humans.
1-Alkyl-2-acetylglycerophosphocholine Esterase
/ blood
Aged
Aged, 80 and over
Aortic Valve
/ enzymology
Aortic Valve Stenosis
/ blood
Biomarkers
/ blood
Calcinosis
/ blood
Case-Control Studies
Europe
Female
Genetic Association Studies
Genetic Predisposition to Disease
Humans
Male
Meta-Analysis as Topic
Phenotype
Polymorphism, Single Nucleotide
Risk Assessment
Risk Factors
Up-Regulation
aortic stenosis
coronary artery disease
Journal
Heart (British Cardiac Society)
ISSN: 1468-201X
Titre abrégé: Heart
Pays: England
ID NLM: 9602087
Informations de publication
Date de publication:
09 2020
09 2020
Historique:
received:
26
02
2020
revised:
18
05
2020
accepted:
26
05
2020
pubmed:
9
7
2020
medline:
29
6
2021
entrez:
9
7
2020
Statut:
ppublish
Résumé
Lipoprotein-associated phospholipase A2 (Lp-PLA2) activity has been shown to predict calcific aortic valve stenosis (CAVS) outcomes. Our objective was to test the association between plasma Lp-PLA2 activity and genetically elevated Lp-PLA2 mass/activity with CAVS in humans. Lp-PLA2 activity was measured in 890 patients undergoing cardiac surgery, including 476 patients undergoing aortic valve replacement for CAVS and 414 control patients undergoing coronary artery bypass grafting. After multivariable adjustment, Lp-PLA2 activity was positively associated with the presence of CAVS (OR=1.21 (95% CI 1.04 to 1.41) per SD increment). We selected four single nucleotide polymorphisms (SNPs) at the Higher Lp-PLA2 activity is significantly associated with the presence of CAVS and might represent a biomarker of CAVS in patients with heart disease. Results of our genetic association study suggest that Lp-PLA2 is however unlikely to represent a causal risk factor or therapeutic target for CAVS.
Sections du résumé
BACKGROUND
Lipoprotein-associated phospholipase A2 (Lp-PLA2) activity has been shown to predict calcific aortic valve stenosis (CAVS) outcomes. Our objective was to test the association between plasma Lp-PLA2 activity and genetically elevated Lp-PLA2 mass/activity with CAVS in humans.
METHODS AND RESULTS
Lp-PLA2 activity was measured in 890 patients undergoing cardiac surgery, including 476 patients undergoing aortic valve replacement for CAVS and 414 control patients undergoing coronary artery bypass grafting. After multivariable adjustment, Lp-PLA2 activity was positively associated with the presence of CAVS (OR=1.21 (95% CI 1.04 to 1.41) per SD increment). We selected four single nucleotide polymorphisms (SNPs) at the
CONCLUSIONS
Higher Lp-PLA2 activity is significantly associated with the presence of CAVS and might represent a biomarker of CAVS in patients with heart disease. Results of our genetic association study suggest that Lp-PLA2 is however unlikely to represent a causal risk factor or therapeutic target for CAVS.
Identifiants
pubmed: 32636298
pii: heartjnl-2020-316722
doi: 10.1136/heartjnl-2020-316722
doi:
Substances chimiques
Biomarkers
0
1-Alkyl-2-acetylglycerophosphocholine Esterase
EC 3.1.1.47
PLA2G7 protein, human
EC 3.1.1.47
Types de publication
Journal Article
Multicenter Study
Observational Study
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1407-1412Subventions
Organisme : Medical Research Council
ID : MC_UU_12015/1
Pays : United Kingdom
Organisme : CIHR
ID : FRN149068
Pays : Canada
Organisme : CIHR
ID : FRN155226
Pays : Canada
Organisme : CIHR
ID : MOP102481
Pays : Canada
Organisme : CIHR
ID : MOP137058
Pays : Canada
Organisme : CIHR
ID : FRN148778
Pays : Canada
Organisme : CIHR
ID : FRN159697
Pays : Canada
Organisme : NHLBI NIH HHS
ID : R01 HL128550
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.
Déclaration de conflit d'intérêts
Competing interests: BA has received research funding from Pfizer, Merck and Ionis Pharmaceuticals and is a consultant for Novartis. PM is a consultant for Casebia Therapeutics.