Abstract 15959: N-6 Polyunsaturated Fatty Acids in RBC Membranes and Estimated Desaturase Activities and Risk of Sudden Cardiac Death
Introduction: Fatty acids in cell membranes modify the propensity for ventricular arrhythmias. In experimental studies, linoleic acid (LA;18:2n-6) has anti-arrhythmic effects, but its association with sudden cardiac death (SCD) risk has been inconsistent. Further, little is known about circulating levels of other n-6 polyunsaturated fatty acids(PUFA) and SCD risk.
Methods: In a case-control analysis nested within 6 prospective cohort studies, we measured RBC levels of LA, γ-linolenic acid (GLA;18:3n-6), dihomo- γ-linoleic acid (DGLA;20:3n-6) and arachiodonic acid (AA; 20:4n-6) in 442 cases of SCD and 852 controls matched on age, sex, race, antecedent CVD, smoking status and fasting status using risk-set sampling. We estimated the activity of 2 key enzymes in n-6 PUFA metabolism, Δ-6desaurase (D6D), which converts LA to GLA, and Δ-5desaturase (D5D), which converts DGLA to AA, using their product to precursor ratios. The multivariable relative risks (RR) were estimated by conditional logistic regression adjusted for other CVD risk factors and n-3 PUFAs in each cohort separately and then combined with random effects meta-analyses.
Results: DGLA was positivity linearly associated with risk of SCD while higher levels of AA were associated with lower risk of SCD. Additionally, higher D5D activity (DGLA/AA), representing greater metabolism of DGLA to AA, was inversely associated with risk (Table). Although LA demonstrated a U-shaped relation, with a nadir in SCD risk in quintile 3, the quadratic relation was not significant (p, quadratic trend = 0.95). Neither GLA nor D6D activity (GLA/LA) were associated with risk of SCD (Table).
Conclusions: Higher RBC DGLA and lower RBC AA were associated with greater risk of SCD and greater estimated activity of the D5D was associated with lower risk. These n-6 PUFAs are not determined by n-6 PUFA intake and thus research on the regulation of DGLA and AA in cell membranes is warranted and may identify novel targets for SCD prevention.
Author Disclosures: S.E. Chiuve: None. N.R. Cook: None. M.V. Moorthy: None. J.M. Gaziano: None. H. Campos: None. C.M. Albert: None.
- © 2015 by American Heart Association, Inc.