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 genomewide association studies of lipidomics (n=4034) and BMI (n=734481), and genetic association analysis of PWD in 5 population-based studies (n=24236). 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

Additional Metadata
Keywords body mass index ◼ genome-wide association study ◼ mass spectrometry ◼ Mendelian randomization analysis ◼ phosphatidylcholine 38:3
Persistent URL dx.doi.org/10.1161/circgen.118.002384, hdl.handle.net/1765/118804
Journal Circulation-Genomic and Precision Medicine
Citation
Del Greco, MF, Foco, L., Teumer, A, Verweij, N, Paglia, G., Meraviglia, V., … Pattaro, C. (2019). Lipidomics, Atrial Conduction, and Body Mass Index Evidence From Association, Mediation, and Mendelian Randomization Models. Circulation-Genomic and Precision Medicine, 12(7). doi:10.1161/circgen.118.002384