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

Citation:
 
Study Design:
Class:
- Click here for explanation of classification scheme.
Quality Rating:
Research Purpose:

To examine the relationship between omega-3 FA intake and atherosclerosis in the carotid arteries of Alaska Eskimos.

 

Inclusion Criteria:
  • Participants in the genetics of coronary artery disease in Alaska natives (GOCADAN) study
  • Males and females 18 years old or older 
  • Inupiat Eskimos from nine villages in the Norton Sound Region of Alaska.  
Exclusion Criteria:

Village residents who were absent on first screening date or those who declined to participate.

Description of Study Protocol:

Recruitment

The study population included 82.6% of age-eligible residents of nine villages (including the town of Nome) in the Norton Sound Region of Alaska who participated in the genetics of coronary artery disease in Alaska natives (GOCADAN) study.

Design

Cross-sectional.

Blinding used 

Outcomes were measured using objective tests.

Statistical Analysis

  • Analysis limited to 686 participants older than age 35 (337 with plaque, 349 without) with valid dietary data (greater than 96% GOCADAN participants with plaque were older than 35 years)
  • Multiple logistic regressions used to evaluate the relationship between intake of each FA (percentage of dietary fat and grams per day calculated for 13 FAs) and the presence of plaque
  • General linear regression models used to evaluate relationship between intake of FAs and average intimal-media thickness (IMT) and plaque score. Plaque score was skewed, so variable normalized by taking the natural logarithm of plaque score +1.
  • All analyses adjusted for age, age two, gender, BMI, smoking status, diabetes and hypertension
  • Data stratified by smoking status at time of interview and each subset reanalyzed to assess whether smoking status influenced the effect of percentage of  fat from a certain FA on arterial phenotypes (IMT, plaque and plaque score).

 

Data Collection Summary:

Timing of Measurements

Measurements or assessments during GOCADAN exam (study examined participants during 2000 to 2004):

  • Blood pressure
  • Ultrasound assessment of carotid artery atherosclerosis
  • ECG
  • Rose questionnaire
  • Blood sampling for TC, TG, HDL, LDL, detailed lipoprotein sub-classification, ApoA1, ApoB, glucose, HgbA1c, fibrinogen, CRP, homocysteine, Lp(a), ApoE genotype, fasting insulin and TSH
  • Urine micro-albumin and creatinine
  • Nutrition interview (FFQ to assess intake during previous year, validated by 24-hour recalls) 
  • Demographic information, data on health habits, dietary intake, quality-of-life, physical activity and medical and reproductive histories
  • Anthropometric measures (height, waist and hip circumference). 

Dependent Variables

  • Carotid artery plaque: Assessed by ultrasound 
  • Plaque score (extent of atherosclerosis): Measured by Doppler recordings, calculated based on number of right and left carotid artery segments containing plaques
  • IMT: Multiple measures made in left and right carotid arteries by electric calipers, then averaged.

Independent Variables

Omega-3 FA intake: Assessed by FFQ and validated by 24-hour recall.

Control Variables

  • Age
  • Gender
  • BMI
  • Smoking status
  • Prevalent diabetes
  • Hypertension.
Description of Actual Data Sample:
  • Initial N: 1,214 (537 males, 677 females) participated in GOCADAN study; 1,131 had ultrasound measures available, of which 686 participants were eligible for this study
  • Attrition (final N): 686
  • Age: Greater than 35 years. Mean, 51; range, 35 to 97 (SD, 11.6).
  • Ethnicity: Predominantly Inupiat Eskimos
  • Other relevant demographics: Many fishermen.

Anthropometrics

  • Average BMI: 27.8 (16.7 to 44.3); SD, 5.7  
  • Waist circumference: 35.1 inches; range, 20 to 57 inches; SD, 5.1.

Location

Norton Sound region of Alaska.

 

Summary of Results:

Fatty Acid Consumption

  • Average intake total n-3 FAs was 4.9g per day (median, 3.7g per day)
  • Average EPA and DHA intake was 2.9g per day
  • Mean total and saturated fat intakes were higher than recommended (previously reported)
  • Mean total intake n-3 FAs was 4.76g per day in those without and 5.07g per day in those with carotid plaque (medians 3.50 and 3.87, respectively, P=0.86 adjusted for age, gender, BMI, smoking, diabetes and hypertension).

Fatty Acid Intake and Measures of Atherosclerosis

  • No significant differences were seen in the prevalence of atherosclerotic plaque or mean plaque score with increasing quartiles of total n-3 FAs or marine n-3 FAs (EPA and DHA)
    • When analyzed as percentage of total fat, EPA and DHA intake and total omega-3 intake were not related to average IMT
    • When analyzed as daily intake of fat, in grams, higher quartiles of total and EPA/DHA intakes were associated with a significantly lower IMT, adjusting for age and gender (both showed decrease of 0.018mm with each increasing quartile of intake). Association remained significant after adjusting for BMI, smoking, hypertension and diabetes.
  • Intake of saturated fat was associated with atherosclerosis measures:
    • When analyzed as percentage of total fat, intake from palmitic or stearic acid was positively associated with the presence of plaque (P=0.04 and P=0.02, respectively) and plaque score (both P=0.02), when adjusted for age and gender
    • When analyzed as fat intake in grams, higher quartiles of either palmitate (P=0.03) or stearate (P=0.03) were associated with significantly higher IMT, when adjusted for age and gender
    • Higher intake of palmitic acid was associated with increased carotid plaque (P=0.01) in multivariate models (adjusted for age, gender, BMI, smoking, prevalent diabetes and hypertension)
  • Odds of prevalent plaque increased with increased intake of palmitic acid (OR=1.25 per quartile of palmitic acid/total fat intake, 95% CI =1.03-1.50, P=0.02) and stearic acid/total fat intake (OR=1.20 per quartile, 95% CI =1.01 to 1.45, P=0.04), after adjusting for standard covariates
  • There was an association between higher plaque score and increasing quartile of stearic acid, but this did not remain statistically significant after adjustment for covariates
  • Increased quartile of palmitic acid intake was significantly associated with higher plaque score (P=0.01)
  • A negative association was found between carotid IMT and intake of either EPA/DHA or palmitate and stearate.

Other Findings

  • Baseline characteristics show that study population was overweight, had a relatively low prevalence of diabetes, low LDL and TG levels, and high HDL levels
  • 56% smoked, which is almost three times greater than the general US population
  • Carotid plaque found in approximately half the study participants
  • Average intake of total and marine n-3 FAs was higher than the amount used in most intervention studies or the recommended intake from the AHA
Author Conclusion:

High intake of omega-3 fatty acids does not protect against plaque formation but is associated with decreased IMT in Inupiat Eskimos in Alaska. High intake of saturated fats, especially palmitic acid, increases plaque formation, even in the presence of large amounts of omega-3 fats.

Funding Source:
Government: NIH Grants RO1-HL64244, U01HL082458, and M10RR0047-34 (GCRC)
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) 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? No
  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? N/A
  3.3. Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.) No
  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? N/A
  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? 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.) Yes
  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? 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? N/A
  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? 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? 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? Yes
  10.2. Was the study free from apparent conflict of interest? Yes