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 association between total, lean and fatty fish consumption and coronary heart disease (CHD) mortality.

Inclusion Criteria:
  • Male
  • Enrolled in the Seven Countries Study and resided in Finland, Italy or the Netherlands
  • Aged 50 to 69 years in 1970
  • Free of CHD around 1970.
Exclusion Criteria:

History of CHD.

Description of Study Protocol:

Men between 50 and 69 years of age were followed for 20 years. Dietary intake was evaluated for the previous six to 12 months using a dietary history and FFQ.

Statistical Analysis

  • To compare baseline risk factors and dietary variables across categories of fish consumption, analysis of variance for normally-distributed variables, the Kruskal-Wallis test for skewed variables and the chi-square test for categorical variables
  • Cox proportional hazards analyses were performed and the analyses were stratified by cohort
  • RR, 95% CI and P-values for linear trend were calculated to investigate the association between fish consumption categories and CHD mortality for each country
  • Fish consumption was not used as a continuous variable, as none of the tests for linear trend supported a linear relationship
  • Adjustments were made for age, cigarette-smoking, BMI, intake of energy and alcohol and consumption of vegetables, fruit, meat, margarine and butter
  • If association of fish consumption with CHD mortality was similar between the countries, data from the three countries were pooled and analyses stratified by cohort
  • Two-tailed significance levels of 0.05 were used.
Data Collection Summary:

Independent Variable: Fish Consumption

  • For each country, subjects were divided into categories based on the number of grams of fish they consumed per day
  • Total fish consumption was determined by adding the number of grams of all fish consumed per day
    • Total and lean fish [less than 10% fat raw or less than 12% fat prepared (plaice, codfish, bream, perch, pike)] consumption (grams per day)
      • None
      • One gram to 19g
      • 20g to 39g
      • 40g or more.
    • Fatty fish (mackerel, herring, eel) comsumption (grams oer day). Only a small proportion consumed fatty fish.
      • None
      • More than zero grams.
    • Canned (sardines, salmon) fish (assigned to neither the lean nor the fatty fish category because of low level of consumption).
  • Food consumption data were collected by using the cross check dietary history method, which was adapted to each country. Provides information about habitual food consumption during the previous six to 12 months.
    • Assessed food consumption pattern during the week and weekends
    • Checklist of foods; the frequencies and quantities of different foods consumed were recorded
    • Compared information between the food consumption pattern and the checklist.

Dependent Variable: Death from CHD

  • Data were collected from death certificates, hospital records or information from the general practitioner, family members and other witnesses to death
  • Coded by one reviewer according to WHO's International Classification of Diseases using standard criteria for interpretation and coding
  • CHD referred to the primary or secondary cause of death according to codes and, when a cardiac origin was mentioned, to the primary cause of sudden cardiac death.
Description of Actual Data Sample:
  • Sample size: N=2,738
    • 1,088 Finish men
    • 1,097 Italian men
    • 553 Dutch men.
  • Final sample size: N=2,738
  • Average age: 58.0 years at baseline.

Baseline Level of Major Risk Factors for CHD According to Categories of Fish Consumption
Mean (SD) for men aged 50 years to 69 years, 1970 to 1990

Country  Fish Consumption
(g per day)
Number

Age (Years)

BMI Systolic Blood Pressure
(mmHg)
Serum Total Cholesterol
(mmol per L)
Smoking (Percentage)
Finland 0-19
476
58.2
(5.7)
24.5
(3.6)
145
(23)
6.77
(1.2)
43.9
20-39
263
57.4
(5.4)
24.6
(3.5)
146
(21)
6.96
(1.33)
51.7
40 or more
349
57.7
(5.4)
24.9
(4.1)
148
(23)
7.18
(140)1
56.21
Italy 0
264
59.1
(5.1)
25.9
(3.7)
153
(21)
5.64
(1.22)
51.5
1-19
347
58.5
(4.7)
25.4
(3.9)
154
(22)
5.67
(1.24)
53.6
20-39
323
57.6
(4.8)
26.0
(4.0)
153
(23)
5.75
(1.13)
48.0
40 or more
163
57.7
(5.2)1
26.1
(4.3)
151
(22)
5.66
(1.13)
50.9
The Netherlands 0
157
58.3
(5.4)
25.4
(2.9)
145
(21)
6.23
(1.15)
55.8
1-19
169
58.6
(5.3)
24.9
(2.3)
145
(19)
6.06
(1.15)
55.8
20 or more
227
58.2
(5.3)
25.1
(2.8)
149
(22)
6.18
(1.08)
50.2

1Statistically different (P<0.05) between fish consumption categories (analysis of variance for normally distributed varieables, chi-square test for dichotomous variables).

Summary of Results:

Baseline Dietary Intake of Various Foods and Other Nutrients, According to Categories of Fish Consumption
Mean (SD)

Foods and Nutrients
Finland
Italy
Netherlands
0-19g
20-39g
40g or more
0g
1-19g
20-39g
40g or more
0g
1-19g
20g or more
Lean Fish (g)
8
(6)
24
(8)
61
(47)*
0
10
(5)
23
(9)
50
(25)*
0
9
(6)
29
(19)*
Fatty Fish (g)
1
(20
5
(8)
23
(29)*
0
2
(4)
4
(8)
7
(18)*
0
2
(4)
3(8)*
Meat (g)
136
(77)
150
(76)
161
(89)*
151
(72)
108
(77)
119
(74)
118
(81)*
138
(44)
139
(44)
143
(41)
Vegetables (g)
66
(48)
84
(66)
94
(68)*
60
(54)
63(51)
72
(50)
80
(60)*
180
(61)
178
(59)
184
(57)
Fruit (g)
158
(164)
191
(233)
184
(173)*
190
(204)
138
(143)
134
(152)
144
(171)*
153
(116)
156
(104)
191
(153)
Alcohol (g)
6
(11)
8
(18)
7
(11)*
7
(53)
81
(60)
87
(57)
91
(66)*
9
(17)
8
(10)
11
(13)
Margarine (g)
3
(8)
3
(7)
4
(10)
8
(13)
16
(6)
16
(16)
16
(15)*
48(21)
53
(22)
56
(25)*
Butter (g)
67
(39)
75
(43)
85
(54)*
15
(14)
8
(14)
7
(12)
6
(12)*
8
(16)
8
(15)
6
(14)
Energy (MJ)
14.9
(4.1)
16.1
(4.8)
16.6
(5.0)*
12.3
(3.3)
11.9
(3.2)
12.6
(3.1)
12.9
(3.3)*
10.6
(2.3)
11.0
(2.1)
11.2
(2.2)*
Protein (Percentage Energy)
12.9
(1.7)
13.0
(1.8)
13.7
(2.0)*
12.0
(2.7)
10.3
(2.8)
10.7
(2.5)
11.1
(2.5)*
2.4
(2.0)
12.4
(1.7)
12.9
(2.0)*
Fat (Percentage Energy)
37.4
(6.7)
36.6
(6.4)
37.9
(7.2)
28.6
(7.6)
27.9
(7.8)
27.4
(7.6)
27.2
(6.8)
40.5
(5.6)
41.7
(4.8)
40.7
(5.3)
Saturated Fat (Percentage Energy)
21.8
(4.5)
21.4
(4.4)
22.1
(5.0)
11.0
(3.6)
9.2
(3.5)
8.8
(3.4)
8.4
(3.4)*
16.9
(3.1)
17.2
(2.8)
16.2
(2.6) *
MUFA (Percentage Energy)
11.5
(2.2)
11.3
(2.1)
11.8
(2.3)*
3.8
(4.3)
15.1
(4.7)
15.3
(4.8)
15.3
(4.2)*
17.1
(3.0)
17.6
(2.6)
17.2
(2.8)
PUFA (Percentage Energy)
2.9
(0.4)
2.8
(0.4)
2.9
(0.5)
3.9
(1.9)
3.6
(2.0)
3.3
(1.4)
3.5
(1.6)*
6.2
(2.0)
6.7
(2.0)
7.1
(2.3)*
Cholesterol
(mg per Day)
641
(248)
685
(256)
762
(285) *
348
(159)
261
(158)
294
(153)
303
(144)*
392
(178)
413
(150)
438
(176)*

*Statistically different (P<0.05) between fish consumption categories (analysis of variance for normally distributed variables, Kruskal-Wallis test for skewed variables).

Relative Risk for 20-Year CHD Mortality, According to Categories of Fish Consumption

Country Fish Consumption (g per Day) Number of Men Number of CHD Deaths
(Percentage)
Mortality Rate* Relative Risk
Crude** Adjusted*** Adjusted§
Finland 0-19
476
100 (21.0)
13.9
1.00
1.00
1.00
20-39
263
52 (19.8)
13.1
0.95
(0.67, 1.34)
0.98
(0.69, 1.40)
0.97
(0.68, 1.38)
At least 40
349
90 (25.8)
18.5
1.39
(1.00, 1.92)
1.31
(0.94, 1.84)
1.25
(0.89, 1.76)
P for trend¶
 
 
 
0.05
0.12
0.2
Italy 0
264
32 (12.1)
8.2
1.00
1.00
1.00
1-19
347
37 (10.7)
7.1
0.87
(0.52, 1.46)
0.93
(0.57, 1.57)
0.94
(0.55, 1.59)
20-39
323
34 (10.5)
6.7
0.81
(0.47, 1.38)
0.99
(0.57, 1.72)
0.93
(.53, 1.63)
At least 40
163
13 (8.0)
5.0
0.56
(0.27, 1.13)
0.69
(0.34, 1.42)
0.67
(0.33, 1.39)
P for trend¶
 
 
 
0.11
0.38
0.33
Netherlands 0
157
29 (18.5)
11.7
1.00
1.00
1.00
1-19
169
30 (17.8)
11.6
1.00
(.60, 1.66)
1.01
(0.60, 1.69)
1.00
(0.59, 1.68)
At least 20
227
46 (20.3)
13.1
1,13
(0.71, 1.80)
1.16
(0.72, 1.86)
1.10
(0.68, 1.79)
P for trend¶
 
 
 
0.60
0.55
0.69

*Per 1,000 person years
**Adjusted for age, BMI, cigarette smoking and energy intake
§Adjusted for age, BMI, cigarette smoking and intake of energy, vegetables, fruit, alcohol, meat, butter and margarine
¶Values for linear trend across categories of total fish consumption
242 mean: (22.2%) died in Finland, 116 (10.6%) in Italy and 105 (19.0%) in the Netherlands.

Adjusted* RR (95% CI) for 20-Year Mortality, According to Categories of Fatty and Lean Fish Consumption

Country Fish Consumption
(g per day)
Number of Men Number of CHD Deaths Adjusted RR
(CI)
Finland Fatty fish 0
697
155
1.00
More than 0
391
87
0.8 (0.51, 1.26)
Lean fish 0
 
 
 
Less than 20
568
124
1.00
At least 20
253
51
0.95 (0.68, 1.33)
At least 40
267
67
1.08 (0.78, 1.5)
P for trend**
 
 
0.63
Italy Fatty fish 0
923
106
1.00
More than 0
174
10
0.4 (0.19, 0.84)
Lean fish 0
318
34
1.00
Less than 20
365
41
1.09 (0.66, 1.81)
At least 20
281
30
0.97 (0.55, 1.69)
At least 40
133
11
0.8 (0.38, 166)
P for trend**
 
 
0.57
Netherlands Fatty fish 0
451
92
1.00
More than 0
102
13
0.70 (0.38, 1.27)
Lean fish 0
216
38
1.00
Less than 20
146
24
0.93 (0.55, 1.55)
At least 20
191
43
1.29 (0.82, 2.03)
At least 40
 
 
 
P for trend**
 
 
0.27

*Adjusted for age, BMI, cigarette-smoking and intake of energy, vegetables, fruit, alcohol, meat, butter and margarine, with fatty and lean fish consmption as dummy variables in one model
**Values for linear trend across categories of lean fish consumption

  • Fish consumption by country
    • Finland
      • Lean fish consumed by 96%
      • Fatty fish consumed by 36%
      • Average: 25±28g per day.
    • Italy
      • Lean fish consumed by 71%
      • Fatty fish consumed by 16%
      • Average: 17±16g per day.
    • Netherlands
      • Lean fish consumed by 61%
      • Fatty fish consumed by 18%
      • Average: 11±9g per day.
  • Pooled data
    • Overall estimated RR for fatty fish consumption, pooled after stratification by cohort, were 0.57 (95% CI: 0.40, 0.80) for one gram to 19g per day and 0.87 (95% CI: 0.59, 1.27) for 20g or more per day, compared with no fatty fish consumption
    • Pooled estimated RR for fatty fish consumers in the three countries was 0.66 (95% CI: 0.49, 0.90)
    • Lean fish intake was not associated with CHD risk in any of the three countries.
Author Conclusion:
  • Pooled results for fatty fish was consistent with a 34% reduction in CHD mortality
  • Results suggest that N-3 fatty acids are responsible for the protective effect of fish.  
Funding Source:
Government: National Institute of Public Health and the Environment (Netherlands)
Industry:
Unilever Research Lab
Food Company:
University/Hospital: Wageningen University, Helsinki University (Iceland), University of Perugia (Italy), University of Kuopio, University of Minnesota
Reviewer Comments:

Authors suggest the protective effect of fatty fish is related to N-3 fatty acids. However, the direct relationship between N-3 fatty acids and CHD mortality was not analyzed because of limited information about the type of fish consumed by cohorts.

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? N/A
  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? 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? N/A
  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? Yes
  6.3. Was the intensity and duration of the intervention or exposure factor sufficient to produce a meaningful effect? Yes
  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? 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? 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? Yes
  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)? Yes
  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? Yes
  8.7. If negative findings, was a power calculation reported to address type 2 error? No
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