He K, Song Y, Daviglus ML, Liu K, Van Horn L, Dyer AR, Greenland P. Accumulated evidence on fish consumption and coronary heart disease mortality: A meta-analysis of cohort studies. Circulation. 2004 Jun 8; 109 (22): 2,705-2,711.

This meta-analyses aimed to assess the dose-response relation between fish consumption and coronary heart disease (CHD) mortality and to explore major sources of heterogeneity among studies.

The criteria for inclusion of studies in the meta-analyses were as follows:

• Studies published between 1966 and 2003 and using prospective cohort study designs
• Studies published only in English
• Relative risks (RR) and their corresponding 95% confident Intervals (CIs) of CHD mortality relating to each category of fish consumption were reported
• Frequency of fish intake was provided (permitted standardizing category of fish consumption).

Criteria for exclusion of any study were as follows:

• Of 18 identified studies, five excluded because they were published as short reports
• Two other studies were excluded because they had only two levels of fish intake (yes vs. no or high vs. low)

• Relevant observational studies were identified by searching: MEDLINE and EMBASE (1966 to 2003)
• Search terms included "fish," "seafood," "omega-3 fatty acids," "n-3 fatty acids," "cardiovascular disease," "fatal coronary heart disease," and "fatal myocardial infarction" (MI)
• Search was restricted to studies using prospective cohort study design and published in English-language journals
• Papers were included if:
  • RRs and their corresponding 95% CIs of CHD mortality relating to each category of fish consumption were reported
  • Frequency of fish intake was provided, which permitted standardizing categorization of fish consumption
• 13 cohorts, eight included only male participants. Number of participants ranged from 852 in the study by Kromhout et al, to 84,688 in the study by Hu et al, 2002.

Design

Meta-analysis of Cohort studies

Dietary Intake/Dietary Assessment Methodology

• Range of follow-up period: Six to 30 years; average duration of follow-up was 11.8 years
• Data on fish consumption collected using self-administered food-frequency questionnaires (FFQ) (seven cohorts) or in-person interview (six cohorts)
• Fish intake was standardized and classified into five intervals
  • Never or less than one per month
  • One to three per month
  • One per week
  • Two to four per week
  • More than five per week.

Blinding Used

Not applicable.

Intervention

Not applicable.

Statistical Analysis

• Publication bias was assessed by using a Begg’s modified funnel plot, in which the RR was plotted on a logarithmic scale against its corresponding SE for each study
• Publication bias was also assessed by two formal tests: The Begg-adjusted rank correlation test and the Egger’s regression asymmetry test
• All analyses were performed with the use of the STATA statistical software (Version 7.0, STATA Corp).

• Timing of measurements: Not applicable
• Dependent variables: CHD mortality
• Independent variables: Fish consumption
• Control variables: Fish intake categories.

• Initial N: 13 cohorts, N=222,364
• Attrition (final N): Same
• Age range: 30-79 years
• Ethnicity: Vary
• Other relevant demographics: Not applicable
• Anthropometrics: Not applicable
• Location:
  • USA
  • UK
  • Netherlands
  • Finland
  • Denmark
  • Italy
  • China.

• Beneficial effects on CHD mortality gradually increased as a function of fish consumption
• Compared with those who never consumed fish or ate fish less than once per month, individuals who ate fish once per week had significantly lower CHD mortality rates (pooled multivariate RR, 0.85; 95% CI, 0.76 to 0.96)
• Individuals who ate fish five or more times per week, CHD mortality was lower by 38% (RR, 0.62; 95% CI, 0.46 to 0.82)
• In five included studies that presented data on non-fatal MI, pooled RRs across five categories of fish intake were 1.0;0.88 (95% CI, 0.70 to 1.10), 0.95 (95% CI, 0.75 to 1.22), 0.86 (95% CI, 0.67 to 1.09) and 0.79 (95% CI, 0.64 to 0.99; P for trend=0.40) for non-fatal MI.

*Men included six studies with 100% male participants; women included four studies (100%, 62%, 62% and 61% women, respectively) with 88% female participants; Osler’s study was not included in either group (women, 47%).

Other Findings

• In stratified analyses, gender did not appear to materially modify the inverse association between fish intake and CHD mortality
• Inverse associations were more evident among those studies with a follow-up of 12 years or longer.

• Authors found a consistently inverse association between fish consumption and CHD mortality rates. The results suggested that eating fishonce per week might significantly reduce death from CHD by 15%
• A dose-response relation was evident between fish consumption and risk of CHD mortality. An increment of 20g per day of fish intakecould possibly lower CHD mortality rates by 7%
• The inverse association was more apparent among studies with a follow-up period of 12 years or longer. On the basis of the available data, the beneficial effects of fish intake on CHD mortality rates were not materially modified by gender or methods of dietary assessment.

• Analyses are based on observational studies, and the inherent limitations of such studies may affect findings. Possibility of residual confounding or bias including measurement errors cannot be excluded
• Dietary assessment, the number of exposure categories, and the reference group varied across individual studies and differences might lead to difficulties in estimating the true effect
• Results were likely to be affected by misclassification of fish intake
• Seven of 18 relevant published studies were excluded, because the presentation of results was too uninformative to allow extraction of a credible effect estimate or weight and the possibility that the findings were affected by the exclusion cannot be completely ruled out.