EAL

DLM: Omega-3 Fatty Acids (2009-2010)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To investigate the relationship between the concentration of n-3 PUFA in serum phospholipids and the number of ventricular arrhythmic events in patients with ischaemic heart disease (IHD) who have an implantable cardioverter defibrillator (ICD).

Inclusion Criteria:

Patients with IHD and an ICD treated in outpatient clinics.

Exclusion Criteria:

Patients with known diabetes, atrial flutter or fibrillation.

Description of Study Protocol:

Recruitment

Patients with an ICD treated in the outpatient clinics at the department of cardiology, Aalborg Hospital, Arhus University Hospital and Skejby Hospital were asked to participate in the study.

Design

Cross-sectional.

Statistical Analysis

Non-paired T-test used for continuous variables (mean and SD)
Chi square or Fishers Exact test used for discrete variables and frequencies
Mantel-Haenszel Chi square test used to assess dose-response.

Data Collection Summary:

Timing of Measurements

Fasting blood samples taken in the am at the end of the 12-month observation period
- Total lipids extracted from serum; phospholipids separated
- N-3 PUFA measured by gas chromatography and expressed as percentile total fatty acids (EPA, DHA, and total n-3 PUFA measured)
ICD stored episodes of ventricular fibrillation (VF) and ventricular tachycardia (VT) registered for 12 months.

Dependent Variables

Incidence of ventricular arrhythmic events (VF and VT).

Independent Variables

Serum n-3 PUFAs.

Control Variables

Age
Sex.

Description of Actual Data Sample:

Initial N: 98 (90 males, eight females)
Attrition (final N): 98
Age: Mean age, 64.5 years
Ethnicity: Danish
Other: 92 patients had a prior myocardial infarction (MI), 36 had prior coronary artery bypass grafting (CABG) and mean left ventricular ejection fraction was 38%. These measures were similar across groups (quintiles of n-3 PUFA intake). The majority of patients were on medications such as beta-blockers, ACE-inhibitors, statins, amiodarone and spironolactone. Medication use was similar across groups.
Location: Denmark.

Summary of Results:

n-3 Fatty Acids and Number of Arrhythmias after Dividing into Quintiles of Total Marine n-3 PUFA in Serum Phospholipids

	First	Second	Third	Fourth	Fifth	All
n-3 Fatty Acids
EPA (%)	1.2 (0.4)	1.8 (0.3)	2.1 (0.4)	2.6 (0.5)	4.1 (1.4)	2.4 (1.2)
DHA (%)	3.5 (0.9)	5.0 (0.4)	5.7 (0.6)	6.7 (0.5)	7.8 (1.1)	5.7 (1.6)
Arrhythmias
Mean No. VT	0.55 (1.3)	0.95 (2.9)	0.22 (0.9)	0.11 (0.3)	0.16 (0.5)	0.35 (1.1)
Mean No. VF	0.75 (1.5)	0.40 (1.6)	0.22 (0.7)	0.22 (0.7)	0.05 (0.2)*	0.41 (1.5)
No. Patients with Arrhythmias	7	6**	2	4	3	22

* P<0.05 (First vs. fifth quintile).
**P<0.05 (First quintile and second quintile vs. other quintiles, Fishers exact test).

Patients Characterized by Number of Ventricular Events and Serum Phospholipid Levels n-3 PUFA

	No Ventricular Arrhythmia	One Ventricular Arrhythmias	More Than One Ventricular Arrhythmias
N	76	22	14
n-3 PUFAs
EPA (%)	2.4 (1.3)	2.0 (1.0)	1.7 (0.9)*
DHA (%)	5.8 (1.6)	5.2 (1.8)	4.5 (1.5)**
Total	9.2 (2.7)	8.2 (2.8)	7.1 (2.4)**

*P<0.04 (Compared to patients with no arrhythmias)
**P<0.01 (Compared to patients with no arrhythmias).

Other Findings

Highly significant positive association found between reported fish intake and n-3 PUFA level in serum phospholipids
Total of 32 VF events and 39 VT events in 22 patients (25%) during 12-month observation (76 patients had no events)
Patients with lowest n-3 PUFA levels had six times greater mean number VF and VT compared to patients with the highest n-3 PUFA levels (1.3 vs. 0.2, respectively)
There was a significant trend (dose-response) towards higher frequency of ventricular arrhythmias among patients with lower levels n-3 PUFA (P=0.02)
N-3 PUFA levels similar in patients taking or not taking statins.

Author Conclusion:

Patients with low plasma marine n-3 PUFAs (EPA and DHA) had a significantly higher incidence of ventricular arrhythmias than patients with high plasma marine n-3 PUFA levels. This suggests that protection offered by marine n-3 PUFAs on sudden cardiac death in previous studies may be due to antiarrhythmic effects.

Funding Source:

Reviewer Comments:

Quality Criteria Checklist: Primary Research
Relevance Questions
	1.	Would implementing the studied intervention or procedure (if found successful) result in improved outcomes for the patients/clients/population group? (Not Applicable for some epidemiological studies)	N/A
	2.	Did the authors study an outcome (dependent variable) or topic that the patients/clients/population group would care about?	Yes
	3.	Is the focus of the intervention or procedure (independent variable) or topic of study a common issue of concern to dieteticspractice?	Yes
	4.	Is the intervention or procedure feasible? (NA for some epidemiological studies)	N/A

Validity Questions
1.	Was the research question clearly stated?		Yes
	1.1.	Was (were) the specific intervention(s) or procedure(s) [independent variable(s)] identified?	Yes
	1.2.	Was (were) the outcome(s) [dependent variable(s)] clearly indicated?	Yes
	1.3.	Were the target population and setting specified?	Yes
2.	Was the selection of study subjects/patients free from bias?		Yes
	2.1.	Were inclusion/exclusion criteria specified (e.g., risk, point in disease progression, diagnostic or prognosis criteria), and with sufficient detail and without omitting criteria critical to the study?	Yes
	2.2.	Were criteria applied equally to all study groups?	Yes
	2.3.	Were health, demographics, and other characteristics of subjects described?	Yes
	2.4.	Were the subjects/patients a representative sample of the relevant population?	Yes
3.	Were study groups comparable?		Yes
	3.1.	Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT)	Yes
	3.2.	Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline?	Yes
	3.3.	Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.)	N/A
	3.4.	If cohort study or cross-sectional study, were groups comparable on important confounding factors and/or were preexisting differences accounted for by using appropriate adjustments in statistical analysis?	Yes
	3.5.	If case control study, were potential confounding factors comparable for cases and controls? (If case series or trial with subjects serving as own control, this criterion is not applicable.)	Yes
	3.6.	If diagnostic test, was there an independent blind comparison with an appropriate reference standard (e.g., "gold standard")?	N/A
4.	Was method of handling withdrawals described?		Yes
	4.1.	Were follow-up methods described and the same for all groups?	N/A
	4.2.	Was the number, characteristics of withdrawals (i.e., dropouts, lost to follow up, attrition rate) and/or response rate (cross-sectional studies) described for each group? (Follow up goal for a strong study is 80%.)	N/A
	4.3.	Were all enrolled subjects/patients (in the original sample) accounted for?	Yes
	4.4.	Were reasons for withdrawals similar across groups?	N/A
	4.5.	If diagnostic test, was decision to perform reference test not dependent on results of test under study?	N/A
5.	Was blinding used to prevent introduction of bias?		Yes
	5.1.	In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate?	N/A
	5.2.	Were data collectors blinded for outcomes assessment? (If outcome is measured using an objective test, such as a lab value, this criterion is assumed to be met.)	Yes
	5.3.	In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded?	Yes
	5.4.	In case control study, was case definition explicit and case ascertainment not influenced by exposure status?	N/A
	5.5.	In diagnostic study, were test results blinded to patient history and other test results?	N/A
6.	Were intervention/therapeutic regimens/exposure factor or procedure and any comparison(s) described in detail? Were interveningfactors described?		Yes
	6.1.	In RCT or other intervention trial, were protocols described for all regimens studied?	N/A
	6.2.	In observational study, were interventions, study settings, and clinicians/provider described?	N/A
	6.3.	Was the intensity and duration of the intervention or exposure factor sufficient to produce a meaningful effect?	N/A
	6.4.	Was the amount of exposure and, if relevant, subject/patient compliance measured?	N/A
	6.5.	Were co-interventions (e.g., ancillary treatments, other therapies) described?	N/A
	6.6.	Were extra or unplanned treatments described?	N/A
	6.7.	Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups?	N/A
	6.8.	In diagnostic study, were details of test administration and replication sufficient?	Yes
7.	Were outcomes clearly defined and the measurements valid and reliable?		Yes
	7.1.	Were primary and secondary endpoints described and relevant to the question?	Yes
	7.2.	Were nutrition measures appropriate to question and outcomes of concern?	Yes
	7.3.	Was the period of follow-up long enough for important outcome(s) to occur?	N/A
	7.4.	Were the observations and measurements based on standard, valid, and reliable data collection instruments/tests/procedures?	N/A
	7.5.	Was the measurement of effect at an appropriate level of precision?	Yes
	7.6.	Were other factors accounted for (measured) that could affect outcomes?	Yes
	7.7.	Were the measurements conducted consistently across groups?	Yes
8.	Was the statistical analysis appropriate for the study design and type of outcome indicators?		Yes
	8.1.	Were statistical analyses adequately described and the results reported appropriately?	Yes
	8.2.	Were correct statistical tests used and assumptions of test not violated?	Yes
	8.3.	Were statistics reported with levels of significance and/or confidence intervals?	Yes
	8.4.	Was "intent to treat" analysis of outcomes done (and as appropriate, was there an analysis of outcomes for those maximally exposed or a dose-response analysis)?	N/A
	8.5.	Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)?	No
	8.6.	Was clinical significance as well as statistical significance reported?	No
	8.7.	If negative findings, was a power calculation reported to address type 2 error?	N/A
9.	Are conclusions supported by results with biases and limitations taken into consideration?		Yes
	9.1.	Is there a discussion of findings?	Yes
	9.2.	Are biases and study limitations identified and discussed?	Yes
10.	Is bias due to study's funding or sponsorship unlikely?		Yes
	10.1.	Were sources of funding and investigators' affiliations described?	No
	10.2.	Was the study free from apparent conflict of interest?	Yes