Discussion
arrhythmias, LVH
CARDIAC ARRHYTHMIAS, SECONDARY, EVENTS, LVH, ARRHYTHMIAS
In this randomized controlled trial, supplementation with omega-3 FA (1 g of EPA + DHA per day) caused several nominally significant changes in ECG parameters over 2-years of follow-up. The PR interval significantly increased and the P-wave duration decreased to a lesser extent in patients randomized to EPA + DHA as compared to placebo. There were also borderline significant net positive differences in change in P-wave amplitude and logarithm of RMSSD in the Omega-3 FA supplementation arm. In the Vitamin D supplementation arm, the Cornell mV, a measure of LVH, increased to a lesser degree than what was observed in the placebo arm. The remainder of the ECG parameters tested did not change with treatment assignment. These observations are novel and provide mechanistic insight on the potential electrophysiologic impact of these commonly used supplements.Epidemiological data have long provided evidence for an inverse relationship between fish consumption, omega-3 FA, and SCDIn secondary analyses, we found that the effect of EPA + DHA supplementation on the PR interval was modified by baseline level of EPA + DHA, such that the change in the PR interval was greater in those with EPA + DHA level below the median and the effect was not significant in those above the median, suggesting there may be a threshold effect. Also, we observed that change in EPA + DHA level was strongly associated with change in the PR interval, and when included in the same multivariable model, appeared to mediate the treatment effect consistent with a potential causal association. However, these findings have not been adjusted for multiple comparisons and should be interpreted with caution and considered hypothesis generating.The PR interval is not only reflective of vagal tone but is also representative of atrial and AV nodal conduction. Omega-3 FA supplementation also had a statistically significant effect on For vitamin D supplementation, we found a marginal protective association between randomized treatment with Vitamin D and progression of LVH on ECG at 2 years, as Cornell voltage increased in both treatment arms, but to a significantly lesser extent in those treated with Vitamin D. These findings are consistent with experimental studies demonstrating direct antihypertrophic actions of the Vitamin D receptor signaling system in cardiomyocytesStrengths of this study include the blinded randomized controlled trial design, sample size, a meaningful proportion of African American enrollees, and high rates of adherence with study medications. There are also several limitations to these data. First, it should be acknowledged that this trial tested one specific preparation and dose of omega-3 FA and vitamin D3; and therefore, dose-dependent effects may have gone undetected. Second, we only investigated common, clinically used ECG measures previously associated with arrhythmic events. Thus, it is possible that we might have missed changes in other less standard measures of cardiac conduction, repolarization and/or electrical heterogeneity. Third, follow-up ECGs were only available at one time-point (year 2), limiting the conclusions that can be derived from the data. In particular, we may have missed changes in the ECG reflecting structural alterations that might have required a longer duration of treatment. Fourth, we can’t rule out repeatability issues with the possibility of normal fluctuation of the ECG measures over timeIn conclusion, two years of treatment with omega-3 FA supplementation (1 g EPA/DHA per day) resulted in changes on the ECG that are potentially reflective of heightened vagal tone and/or slowing of intraatrial and AV conduction; whereas, treatment with Vitamin D3 (2000 IU per day) may have exhibited an antihypertrophic effect. These results suggest that these commonly used supplements may have subtle effects on cardiac electrophysiology even at low dosages which may influence, both favorably and adversely, the propensity toward cardiac arrhythmias. Whether such subtle effects could ultimately impact risk for arrhythmias in clinical practice is unknown and requires further study.