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 Dörr; Harold Snieder; James F Wilson; Peter P Pramstaller; Alessandra Rossini; Cristian Pattaro

doi:10.1161/CIRCGEN.118.002384

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

Research output: Contribution to journal › Article › Academic › peer-review

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.

Original language	English
Pages (from-to)	e002384
Journal	Circulation. Genomic and precision medicine
Volume	12
Issue number	7
DOIs	https://doi.org/10.1161/CIRCGEN.118.002384
Publication status	Published - Jul 2019
Externally published	Yes

Keywords

Adult
Aged
Arteries/metabolism
Body Mass Index
Cardiovascular Diseases/metabolism
Electrocardiography
Female
Genome-Wide Association Study
Humans
Lipid Metabolism
Lipidomics
Lipids/chemistry
Male
Mendelian Randomization Analysis
Middle Aged
Risk Factors

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10.1161/CIRCGEN.118.002384

Cite this

Del Greco M, F., Foco, L., Teumer, A., Verweij, N., Paglia, G., Meraviglia, V., Melotti, R., Vukovic, V., Rauhe, W., Joshi, P. K., Demirkan, A., Felix, S. B., Pietzner, M., Said, M. A., van de Vegte, Y. J., van der Harst, P., Wright, A. F., Hicks, A. A., Campbell, H., ... Pattaro, C. (2019). Lipidomics, Atrial Conduction, and Body Mass Index. Circulation. Genomic and precision medicine, 12(7), e002384. https://doi.org/10.1161/CIRCGEN.118.002384

@article{cd2f6cca6eb8421faf6324d62a71b803,

title = "Lipidomics, Atrial Conduction, and Body Mass Index",

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.",

keywords = "Adult, Aged, Arteries/metabolism, Body Mass Index, Cardiovascular Diseases/metabolism, Electrocardiography, Female, Genome-Wide Association Study, Humans, Lipid Metabolism, Lipidomics, Lipids/chemistry, Male, Mendelian Randomization Analysis, Middle Aged, Risk Factors",

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

year = "2019",

month = jul,

doi = "10.1161/CIRCGEN.118.002384",

language = "English",

volume = "12",

pages = "e002384",

number = "7",

}

Del Greco M, F, Foco, L, Teumer, A, Verweij, N, Paglia, G, Meraviglia, V, Melotti, R, Vukovic, V, Rauhe, W, Joshi, PK, Demirkan, A, Felix, SB, Pietzner, M, Said, MA, van de Vegte, YJ, van der Harst, P, Wright, AF, Hicks, AA, Campbell, H, Dörr, M, Snieder, H, Wilson, JF, Pramstaller, PP, Rossini, A & Pattaro, C 2019, 'Lipidomics, Atrial Conduction, and Body Mass Index', Circulation. Genomic and precision medicine, vol. 12, no. 7, pp. e002384. https://doi.org/10.1161/CIRCGEN.118.002384

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

PY - 2019/7

Y1 - 2019/7

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.

AB - 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.

KW - Adult

KW - Aged

KW - Arteries/metabolism

KW - Body Mass Index

KW - Cardiovascular Diseases/metabolism

KW - Electrocardiography

KW - Female

KW - Genome-Wide Association Study

KW - Humans

KW - Lipid Metabolism

KW - Lipidomics

KW - Lipids/chemistry

KW - Male

KW - Mendelian Randomization Analysis

KW - Middle Aged

KW - Risk Factors

U2 - 10.1161/CIRCGEN.118.002384

DO - 10.1161/CIRCGEN.118.002384

M3 - Article

C2 - 31306056

SN - 2574-8300

VL - 12

SP - e002384

JO - Circulation. Genomic and precision medicine

JF - Circulation. Genomic and precision medicine

IS - 7

ER -

Lipidomics, Atrial Conduction, and Body Mass Index

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