EAL

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

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To assess whether dietary consumption of higher amounts of total linolenic acid (alpha- and gamma-form) was associated with QTrr and JTrr and whether such association was modified by the ratio of linoleic-to-linolenic fatty acid.

Inclusion Criteria:

Participation in the NHLBI Family Heart study which required either random selection or a higher than expected risk of CAD.

Exclusion Criteria:

Missing data on ECG, dietary linolenic acid or covariates
Unreliable food frequency questionnaires
Energy intake outside of a priori ranges
Myocardial infarction or major ventricular conduction defect
QRS interval greater than 120ms.

Description of Study Protocol:

Recruitment

Participants of the NHLBI Family Heart study

Design

Cross-sectional

Blinding used

None described

Intervention

None

Statistical Analysis

Gender-, age-, and energy-specific tertiles of linolenic acid were created with four-year age groups and quintiles of energy intake for each gender. Within each of these 35 groupings, tertiles of linolenic acid were created. Adjusted mean values of QTrr and JTrr were estimated by using generalized estimating equations. The minimal adjusted model controlled for age, BMI, systolic and diastolic blood pressure, and serum potassium. The full model also controlled for diabetes mellitus, exercise, class Ia and class III anti-arrhythmic drugs and other drugs known to prolong QT intervals. The 95th percentile of the gender-specific distribution of QTrr and JTrr was used to define abnormal QTrr and JTrr and a generalized estimating equation was used to compute the prevalence odds ratios. Linolenic acid was used as a continuous variable and related to QTrr and JTrr. Alpha level was set at 0.05.

Data Collection Summary:

Timing of Measurements

All measurements were performed a single time

Dependent Variables

ECG: Standard 12-lead using MAC-PC electrocardiographs and 10-s records were digitized using a sampling rate of 250 samples/s per lead. All QT measurements were visually verified. The QT and JT intervals were rate-adjusted as a linear function of the RR interval.
Resting blood pressure: Three times while sitting after a five-minute rest using a random zero sphygmomanometer
Smoking history, alcohol intake, education and physical activity during past year: Interview
Diabetes diagnosis: Taking hypoglycemic agents, MD had told him or fasting glucose greater than 7.0mmol/l.
CAD: Self-reported history of myocardial infaction, percutaneous tranaluminal coronary angioplasty or coronary artery bypass graft
Digoxin, diuretics, anti-arrhythmic drugs and other drugs: Medication inventory.

Independent Variables

Linolenic acid intake assessed by a validated semi-quantitative food frequency questionnaire. Values were obtained from the Harvard University Food Composition Database derived from USDA sources and manufacturer information.

Control Variables

Description of Actual Data Sample:

Initial N (e.g., 731 (298 males, 433 females))

5,710 (gender not described)

Attrition (final N)

3,642 (1,477 males and 2,165 females)

Age

48.6±13.4 for men and 51.1±13.4 for women

Ethnicity

Caucasian

Other relevant demographics

Anthropometrics (e.g., were groups same or different on important measures)

Location

Various sites in the United States

Summary of Results:

Findings

The average daily intake of dietary linolenic acid was 0.81±0.35g for men (range 0.21-3.48 grams per day) and 0.69±0.29g for women (range 0.13-2.45 grams per day).

Dietary linolenic acid was inversely associated with QTrr in men in a multi-variable adjusted model (P for linear trend 0.0009). In women, a non-statistically significant inverse association between dietary linolenic acid and QTrr was observed (P for trend 0.12).

In a multi-variable model, both men and women showed an inverse association between linolenic acid and JTrr in a dose-response fashion (P for linear trend 0.002 for men and 0.04 for women).

There was evidence for a reduced risk for the prolonged repolarization in both men and women. From the lowest to the highest tertile of linolenic acid, multi-variable adjusted prevalence odds ratios for prolonged repolarization based on QTrr were 1.0 (reference), 0.81 (95% confidence intervals [CI] 0.46 to 1.44), and 0.51 (95% CI 0.27 to 0.98), respectively, for men (P for trend 0.04). Corresponding values for women were 1.0, 0.71 (95% CI 0.53 to 0.95 (text states 00.95), and 0.60 (95% CI 0.44 to 0.82), respectively (P for trend 0.003). Similar reduced risk of prolonged repolarization using JTrr was observed, and the results were stronger in women than in men. In both men and women combined, the risk of abnormally prolonged repolarization was 41% lower in the highest tertile of linolenic acid compared with the lowest tertile in a multi-variable adjusted model.

The ratio of linoleic-to-linolenic acid did not influence the results, and there was no evidence for interaction between linoleic and linolenic acid on abnormal QTrr (P=0.21) or JTrr (P=0.23).

Exclusion of subjects currently receiving digoxin or anti-arrhythmic drugs did not change the results. In a sample that included subjects excluded in the initial analyses (prevalent CAD, left ventricular hypertrophy, etc), the observed association persisted.

Author Conclusion:

A higher consumption of dietary linolenic acid is associated with a reduced risk of prolonged repolarization in both men and women.

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)	Yes
	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)	Yes

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.)	Yes
	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.)	N/A
	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?	Yes
	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%.)	Yes
	4.3.	Were all enrolled subjects/patients (in the original sample) accounted for?	Yes
	4.4.	Were reasons for withdrawals similar across groups?	???
	4.5.	If diagnostic test, was decision to perform reference test not dependent on results of test under study?	Yes
5.	Was blinding used to prevent introduction of bias?		No
	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.)	No
	5.3.	In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded?	No
	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?	Yes
	6.3.	Was the intensity and duration of the intervention or exposure factor sufficient to produce a meaningful effect?	???
	6.4.	Was the amount of exposure and, if relevant, subject/patient compliance measured?	Yes
	6.5.	Were co-interventions (e.g., ancillary treatments, other therapies) described?	Yes
	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?	Yes
	6.8.	In diagnostic study, were details of test administration and replication sufficient?	N/A
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?	???
	7.4.	Were the observations and measurements based on standard, valid, and reliable data collection instruments/tests/procedures?	Yes
	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)?	Yes
	8.6.	Was clinical significance as well as statistical significance reported?	N/A
	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?	Yes
	10.2.	Was the study free from apparent conflict of interest?	Yes