Tags

Type your tag names separated by a space and hit enter

Lipidomics, Atrial Conduction, and Body Mass Index.
Circ Genom Precis Med 2019; 12(7):e002384CG

Abstract

BACKGROUND

Lipids are increasingly involved in cardiovascular risk prediction as potential proarrhythmic influencers. However, knowledge is limited about the specific mechanisms connecting lipid alterations with atrial conduction.

METHODS

To shed light on this issue, we conducted a broad assessment of 151 sphingo- and phospholipids, measured using mass spectrometry, for association with atrial conduction, measured by P wave duration (PWD) from standard electrocardiograms, in the MICROS study (Microisolates in South Tyrol) (n=839). Causal pathways involving lipidomics, body mass index (BMI), and PWD were assessed using 2-sample Mendelian randomization analyses based on published genome-wide association studies of lipidomics (n=4034) and BMI (n=734 481), and genetic association analysis of PWD in 5 population-based studies (n=24 236).

RESULTS

We identified an association with relative phosphatidylcholine 38:3 (%PC 38:3) concentration, which was replicated in the ORCADES (Orkney Complex Disease Study; n=951), with a pooled association across studies of 2.59 (95% CI, 1.3-3.9; P=1.1×10-4) ms PWD per mol% increase. While being independent of cholesterol, triglycerides, and glucose levels, the %PC 38:3-PWD association was mediated by BMI. Results supported a causal effect of BMI on both PWD (P=8.3×10-5) and %PC 38:3 (P=0.014).

CONCLUSIONS

Increased %PC 38:3 levels are consistently associated with longer PWD, partly because of the confounding effect of BMI. The causal effect of BMI on PWD reinforces evidence of BMI's involvement into atrial electrical activity.

Authors+Show Affiliations

Institute for Biomedicine, Eurac Research, Affiliated to the University of Lübeck, Bolzano, Italy (G.P., L.F., R.M., V.V., A.A.H., P.P.P., A.R., C.P.).Institute for Community Medicine (A.T., S.B.F.), University Medicine Greifswald, Germany.Department of Cardiology (N.V., M.A.S., Y.J.v.d.V., P.v.d.H.), University of Groningen, University Medical Center Groningen, The Netherlands.Institute for Biomedicine, Eurac Research, Affiliated to the University of Lübeck, Bolzano, Italy (G.P., L.F., R.M., V.V., A.A.H., P.P.P., A.R., C.P.).Leiden University Medical Center, The Netherlands (V.M.).Institute for Biomedicine, Eurac Research, Affiliated to the University of Lübeck, Bolzano, Italy (G.P., L.F., R.M., V.V., A.A.H., P.P.P., A.R., C.P.).Institute for Biomedicine, Eurac Research, Affiliated to the University of Lübeck, Bolzano, Italy (G.P., L.F., R.M., V.V., A.A.H., P.P.P., A.R., C.P.).Department of Cardiology, San Maurizio Hospital, Bolzano, Italy (W.R.).Centre for Global Health Research, Usher Institute for Population Health Sciences and Informatics (J.F.W., H.C., P.K.J.), University of Edinburgh, Scotland, United Kingdom.Department of Anatomy and Embryology and Department of Human Genetics (A.D.). Genetic Epidemiology Unit, Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands (A.D.).Institute for Community Medicine (A.T., S.B.F.), University Medicine Greifswald, Germany.Institute of Clinical Chemistry and Laboratory Medicine (M.P.), University Medicine Greifswald, Germany. German Centre for Cardiovascular Research (DZHK), Partner Site Greifswald, Germany (M.P., M.D.).Department of Cardiology (N.V., M.A.S., Y.J.v.d.V., P.v.d.H.), University of Groningen, University Medical Center Groningen, The Netherlands.Department of Cardiology (N.V., M.A.S., Y.J.v.d.V., P.v.d.H.), University of Groningen, University Medical Center Groningen, The Netherlands.Department of Cardiology (N.V., M.A.S., Y.J.v.d.V., P.v.d.H.), University of Groningen, University Medical Center Groningen, The Netherlands.MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine (A.F.W., J.F.W.), University of Edinburgh, Scotland, United Kingdom.Institute for Biomedicine, Eurac Research, Affiliated to the University of Lübeck, Bolzano, Italy (G.P., L.F., R.M., V.V., A.A.H., P.P.P., A.R., C.P.).Centre for Global Health Research, Usher Institute for Population Health Sciences and Informatics (J.F.W., H.C., P.K.J.), University of Edinburgh, Scotland, United Kingdom.Department of Internal Medicine B (M.D.), University Medicine Greifswald, Germany. German Centre for Cardiovascular Research (DZHK), Partner Site Greifswald, Germany (M.P., M.D.).Department of Epidemiology (H.S.), University of Groningen, University Medical Center Groningen, The Netherlands.Centre for Global Health Research, Usher Institute for Population Health Sciences and Informatics (J.F.W., H.C., P.K.J.), University of Edinburgh, Scotland, United Kingdom. MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine (A.F.W., J.F.W.), University of Edinburgh, Scotland, United Kingdom.Institute for Biomedicine, Eurac Research, Affiliated to the University of Lübeck, Bolzano, Italy (G.P., L.F., R.M., V.V., A.A.H., P.P.P., A.R., C.P.).Institute for Biomedicine, Eurac Research, Affiliated to the University of Lübeck, Bolzano, Italy (G.P., L.F., R.M., V.V., A.A.H., P.P.P., A.R., C.P.).Institute for Biomedicine, Eurac Research, Affiliated to the University of Lübeck, Bolzano, Italy (G.P., L.F., R.M., V.V., A.A.H., P.P.P., A.R., C.P.).

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31306056

Citation

Del Greco M, Fabiola, et al. "Lipidomics, Atrial Conduction, and Body Mass Index." Circulation. Genomic and Precision Medicine, vol. 12, no. 7, 2019, pp. e002384.
Del Greco M F, Foco L, Teumer A, et al. Lipidomics, Atrial Conduction, and Body Mass Index. Circ Genom Precis Med. 2019;12(7):e002384.
Del Greco M, F., Foco, L., Teumer, A., Verweij, N., Paglia, G., Meraviglia, V., ... Pattaro, C. (2019). Lipidomics, Atrial Conduction, and Body Mass Index. Circulation. Genomic and Precision Medicine, 12(7), pp. e002384. doi:10.1161/CIRCGEN.118.002384.
Del Greco M F, et al. Lipidomics, Atrial Conduction, and Body Mass Index. Circ Genom Precis Med. 2019;12(7):e002384. PubMed PMID: 31306056.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Lipidomics, Atrial Conduction, and Body Mass Index. AU - Del Greco M,Fabiola, AU - Foco,Luisa, AU - Teumer,Alexander, AU - Verweij,Niek, AU - Paglia,Giuseppe, AU - Meraviglia,Viviana, AU - Melotti,Roberto, AU - Vukovic,Vladimir, AU - Rauhe,Werner, AU - Joshi,Peter K, AU - Demirkan,Ayse, AU - Felix,Stephan B, AU - Pietzner,Maik, AU - Said,M Abdullah, AU - van de Vegte,Yordi J, AU - van der Harst,Pim, AU - Wright,Alan F, AU - Hicks,Andrew A, AU - Campbell,Harry, AU - Dörr,Marcus, AU - Snieder,Harold, AU - Wilson,James F, AU - Pramstaller,Peter P, AU - Rossini,Alessandra, AU - Pattaro,Cristian, Y1 - 2019/07/15/ PY - 2019/7/16/entrez PY - 2019/7/16/pubmed PY - 2019/7/16/medline KW - Mendelian randomization analysis KW - body mass index KW - genome-wide association study KW - mass spectrometry KW - phosphatidylcholine 38:3 SP - e002384 EP - e002384 JF - Circulation. Genomic and precision medicine JO - Circ Genom Precis Med VL - 12 IS - 7 N2 - BACKGROUND: Lipids are increasingly involved in cardiovascular risk prediction as potential proarrhythmic influencers. However, knowledge is limited about the specific mechanisms connecting lipid alterations with atrial conduction. METHODS: To shed light on this issue, we conducted a broad assessment of 151 sphingo- and phospholipids, measured using mass spectrometry, for association with atrial conduction, measured by P wave duration (PWD) from standard electrocardiograms, in the MICROS study (Microisolates in South Tyrol) (n=839). Causal pathways involving lipidomics, body mass index (BMI), and PWD were assessed using 2-sample Mendelian randomization analyses based on published genome-wide association studies of lipidomics (n=4034) and BMI (n=734 481), and genetic association analysis of PWD in 5 population-based studies (n=24 236). RESULTS: We identified an association with relative phosphatidylcholine 38:3 (%PC 38:3) concentration, which was replicated in the ORCADES (Orkney Complex Disease Study; n=951), with a pooled association across studies of 2.59 (95% CI, 1.3-3.9; P=1.1×10-4) ms PWD per mol% increase. While being independent of cholesterol, triglycerides, and glucose levels, the %PC 38:3-PWD association was mediated by BMI. Results supported a causal effect of BMI on both PWD (P=8.3×10-5) and %PC 38:3 (P=0.014). CONCLUSIONS: Increased %PC 38:3 levels are consistently associated with longer PWD, partly because of the confounding effect of BMI. The causal effect of BMI on PWD reinforces evidence of BMI's involvement into atrial electrical activity. SN - 2574-8300 UR - https://www.unboundmedicine.com/medline/citation/31306056/Lipidomics,_Atrial_Conduction,_and_Body_Mass_Index L2 - http://www.ahajournals.org/doi/full/10.1161/CIRCGEN.118.002384?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -