Lipidomics, Atrial Conduction, and Body Mass Index

Fabiola Del Greco M, Luisa Foco, Alexander Teumer, Niek Verweij, Giuseppe Paglia, Viviana Meraviglia, Roberto Melotti, Vladimir Vukovic, Werner Rauhe, Peter K Joshi, Ayse Demirkan, Stephan B Felix, Maik Pietzner, M Abdullah Said, Yordi J van de Vegte, Pim van der Harst, Alan F Wright, Andrew A Hicks, Harry Campbell, Marcus DörrHarold Snieder, James F Wilson, Peter P Pramstaller, Alessandra Rossini, Cristian Pattaro

OnderzoeksoutputAcademicpeer review

5 Citaten (Scopus)

Samenvatting

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.

Originele taal-2English
Artikelnummere002384
Aantal pagina's11
TijdschriftCirculation. Genomic and precision medicine
Volume12
Nummer van het tijdschrift7
DOI's
StatusPublished - jul-2019

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