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.
U2 - 10.1161/CIRCGEN.118.002384
DO - 10.1161/CIRCGEN.118.002384
M3 - Article
C2 - 31306056
SN - 2574-8300
VL - 12
JO - Circulation. Genomic and precision medicine
JF - Circulation. Genomic and precision medicine
IS - 7
M1 - e002384
ER -