VITAL Rhythm Study

Atrial fibrillation and sudden cardiac death assessments, as well as blood analyses, will be
conducted on the entire VITAL Study population, and ECG analyses will be limited to the
Clinical and Translational Science Center (CTSC) sub-cohort of 1,054 VITAL participants who
live near the Boston area and agree to participate in a series of ancillary studies in
addition to the main trial.

Investigators will ascertain atrial fibrillation events utilizing self-report of physician
diagnoses of atrial fibrillation received on annual questionnaires from study participants
supplemented by outpatient and hospital visits for AF identified through Centers for Medicare
and Medicaid Services (CMS) data linkage. Investigators will also ascertain additional
information regarding atrial fibrillation diagnosis from supplementary questionnaires, and
seek consent to review all inpatient and outpatient hospital records pertaining to atrial
fibrillation diagnosis and evaluation. Atrial fibrillation events will be confirmed by an
endpoint committee composed of cardiologists, which will also make a determination on atrial
fibrillation subtype and pattern. An intention-to-treat analysis examining the main effects
of omega-3 fatty acids and vitamin D on incident atrial fibrillation will be performed to
address the primary aims.

Electrocardiograms will be obtained at baseline and again after two years of treatment and
follow-up among a sub-cohort of 1,054 patients being enrolled in VITAL at the CTSC.
Investigators will utilize these ECG data to evaluate whether treatment with omega-3 fatty
acids and vitamin D3 have significant effects on ECG measures. The ECGs will also be utilized
to estimate the prevalence of asymptomatic persistent atrial fibrillation in our population
not detected by our atrial fibrillation surveillance methods.

Investigators will examine baseline blood samples for an estimated 500 participants with
confirmed atrial fibrillation for the purpose of exploring whether the effect of vitamin D3
or fish oil supplementation on atrial fibrillation risk varies by the baseline blood levels
of these nutrients.

Investigators will also seek additional information necessary to classify deaths as sudden or
arrhythmic in origin, and cardiac deaths will be reviewed by an endpoint committee of
cardiologists. Once these results have been compiled investigators will explore whether
omega-3 fatty acids and/or vitamin D might have an effect on sudden and/or arrhythmic cardiac
death.

To be eligible this ancillary study participants must be enrolled in the Vitamin D and
Omega-3 Trial (VITAL; National Clinical Trial (NCT) 01169259) and meet the following
criteria:

Inclusion Criteria:

- physician diagnosis of atrial fibrillation after randomization

and/or

- cardiovascular death

Exclusion Criteria:

- physician diagnosis of atrial fibrillation prior to randomization