Consumption of dietary long-chain omega-3 fatty acids and cardiovascular disease.

Long-chain omega-3 fatty acids and total cardiovascular disease (CVD).

Results: Data was provided by 5 cohorts, including 6,620 cases. In all cases only fatty acids from seafood were examined.
A significant protective effect was found in one cohort of small size (Dolecek TA [12]), and a nonsignificant protective effect (RR, but not the trend) was found among women in another cohort of small size (Nagata C [23]). No other associations were found. RR's were available from 4 cohorts. The average RR = 1.05.
Effect modification: No data was found.
Subjects with prevalent disease: No data was found.

Conclusion: some protective effects were found, but these were restricted to cohorts of small size, and the average effect size does not support the possibility of a protective effect. No evidence was found for an association between consumption of dietary long-chain omega-3 fatty acids and total cardiovascular disease.

Prospective studies of dietary long-chain omega-3 and total cardiovascular disease:
AuthorCohort nameCasesEnd pointRelative Risk (RR)
23) Nagata C (2002)The Takayama Study308 men, and

327 women
MortalityMen: HR = 0.76 (0.54-1.07; P = 0.27).

Women: HR = 0.77 (0.55-1.00; P = 0.16)
22) Folsom AR (2004)The Iowa Women's Health Study1,589MortalityNo significant association.
17) Morris MC (1995)The Physician's Health Study525RiskRR = 1.1 (0.8-1.5; P = 0.63).
13) Virtanen JK (2008)The Health Professionals Follow-up Study3,639RiskRR = 1.12 (0.92-1.36; P = 0.16).
12) Dolecek TA (1992)The Multiple Risk Factor Intervention Trial232MortalityRR = 0.60 (P = 0.01).
Total number of cases: 6,620Average RR = 1.05

Long-chain omega-3 fatty acids and coronary heart disease (CHD).

Results:
Coronary heart disease risk: Data was provided about 17 cohorts, including 9,012 cases.
Significant protective effects were found in 7 cohorts (Dolecek TA [12], Hu FB [13], Albert CM [17], Yuan JM [20], Mozaffarian D [27], Iso H [36], de Goede J [44]), including 2,521 cases (28% of all cases). The RR, but not the trend was significant in two of these cohorts (Albert CM [17], Iso H [36]). RR's were available from 15 cohorts. The average RR = 0.87.
When coronary-artery bypass-grafting is included as CHD (Ascherio A [13]), the total amount of cases increases to 9,744, and the average RR is attenuated to 0.92.
Coronary heart disease mortality: Data was provided by 16 cohorts, including 4,608 cases.
Significant protective effects were found in 6 cohorts (Dolecek TA [12], Hu FB [13], Albert CM [17], Yuan JM [20], Mozaffarian D [27], de Goede J [44]), including 1,135 cases (25% of all cases). But a significantly increased risk (RR, but not trend) was found in another cohort (Pietinen P [19]), including 635 cases. RR's were available from 15 cohorts. The average RR = 0.85.
Heart failure: Data about heart failure risk was provided by 5 cohorts, including 3,179 + X cases (no amount of cases was defined in a subcohort (Levitan EB [42])). A significant protective effect was found in one cohort of very small size, and with a very high prevalence of heart failure (Mozaffarian D [27]). No other associations were found. RR's were available from all cohorts, but not for the subcohort of men with a history of MI or diabetes (Levitan EB [42]). The average RR = 0.81.
Effect modification:

  • Protective effects were equally distributed among men and women, but increased risks were restricted to men. Among data for women the RR for CHD in combination with the amount of cases was provided by only 3 cohorts (Hu FB [13], Järvinen R [15], Nagata C [23]). Therefore no attempt was made to calculate RR's for men vs women.
  • A significant interaction with age was found in one cohort of very small size (Streppel MT [7]), but not in another cohort (de Goede J [44]).
  • No effect modification was found by aspirin use, the ratio omega-6:omega-3 (Hu FB [13]), or intake of N-6 polyunsaturated fat (Mozaffarian D [13]).

Subjects with prevalent disease: A nonsignificant protective effect was found in one cohort including women with type 2 diabetes only (Hu FB [13]). But no association was found in another cohort including subjects with suspected CAD only (Manger MS [46]).

Conclusion: Significant protective effects against CHD risk were found in 7 out of 17 cohorts, but these included only a minority of the total amount of cases. Inconclusive evidence was found for an association between consumption of dietary long-chain omega-3 fatty acids and coronary heart disease risk.
Significant protective effects against CHD mortality were found in 6 out of 16 cohorts, but these included only a minority of the total amount of cases. And a significantly increased risk was found in another cohort which was of moderate size. Inconclusive evidence was found for an association between consumption of dietary long-chain omega-3 fatty acids and coronary heart disease mortality.

Prospective studies of dietary long-chain omega-3 and coronary heart disease risk:
AuthorCohort nameCasesEnd pointRelative Risk (RR)
46) Manger MS (2010)The Western Norway B vitamin Intervention Trial210RiskHR = 1.05 (0.72-1.52).
44) de Goede J (2010)The MORGEN Study82 fatal CHD, and

252 nonfatal MI
Mortality, and

Risk
Mortality: HR = 0.51 (0.27-0.94; P = 0.05).

Nonfatal MI: HR = 1.07 (0.74-1.54; P = 0.18).
44) Joensen AM (2010)The Danish Diet, Cancer and Health Cohort1,124

(no data for men vs women)
RiskMen: HR = 0.81 (0.64-1.04).

Women: HR = 0.97 (0.62-1.52).
39) Yamagishi K (2008)The JACC Study307Heart failure mortalityHR = 0.80 (0.55-1.17; P = 0.13).
38) Kaushik S (2008)The Blue Mountains Eye Study184MortalityHR = 0.79 (0.48-1.29).
36) Iso H (2006)The JPHC Study258RiskHR = 0.58 (0.35-0.97; P = 0.18).
27) Mozaffarian D (2003)The Cardiovascular Health Study247RiskHR = 0.58 (0.38-0.90).
23) Nagata C (2002)The Takayama Study63 men, and

52
MortalityMen: HR = 1.05 (0.56-1.97; P = 0.91).

Women: HR = 0.73 (0.37-1.45; P = 0.37).
22) Folsom AR (2004)The Iowa Women's Health Study922MortalityNo significant association.
20) Yuan JM (2001)The Shanghai Cohort Study113 MI, and

74 other IHD
MortalityMI: RR = 0.43 (0.23-0.81; P = 0.02).

Other IHD: RR = 0.71 (0.32-1.57; P = 0.68).
19) Pietinen P (1997)The ATBC Study1,399RiskRR = 1.15 (0.97-1.35; P = 0.12).
17) Albert CM (1998)The Physician's Health Study133MortalityRR = 0.43 (0.20-0.93; P = 0.21).
17) Morris MC (1995)The Physician's Health Study259Nonfatal MIRR = 1.1 (0.7-1.8; P = 0.99).
15) Järvinen R (2006)The Finnish Mobile Clinic Health Survey335 men, and

163 women
MortalityMen: RR = 0.96 (0.68-1.38; P = 1.00).

Women: RR = 0.73 (0.44-1.19; P = 0.31).
13) Hu FB (2002)The Nurses' Health Study1,513RiskRR = 0.69 (0.57-0.84; P = < 0.001).
13) Ascherio A (1995)The Health Professionals Follow Up Study811RiskRR = 1.09 (0.88-1.35; P = 0.48).
12) Dolecek TA (1992)The Multiple Risk Factor Intervention Trial175MortalityRR = 0.61 (P = < 0.05).
7) Streppel MT (2008)The Zutphen Study336MortalityHR = 0.65 (0.40-1.06).
Total number of cases: 9,012Average RR = 0.87


Prospective studies of dietary long-chain omega-3 and coronary heart disease mortality:
AuthorCohort nameCasesEnd pointRelative Risk (RR)
46) Manger MS (2010)The Western Norway B vitamin Intervention Trial76CHDHR = 1.33 (0.67-2.62; P = 0.79).
44) de Goede J (2010)The MORGEN Study82CHDHR = 0.51 (0.27-0.94; P = 0.05).
39) Yamagishi K (2008)The JACC Study307Heart failureHR = 0.80 (0.55-1.17; P = 0.13).
38) Kaushik S (2008)The Blue Mountains Eye Study184CHDHR = 0.79 (0.48-1.29).
36) Iso H (2006)The JPHC Study62CHDHR = 1.54 (0.60-3.99; P = 0.10).
27) Mozaffarian D (2003)The Cardiovascular Health Study148Arrhytmic IHDHR = 0.45 (0.25-0.81).
23) Nagata C (2002)The Takayama Study63 men, and

52
IHDMen: HR = 1.05 (0.56-1.97; P = 0.91).

Women: HR = 0.73 (0.37-1.45; P = 0.37).
22) Folsom AR (2004)The Iowa Women's Health Study922CHDNo significant association.
20) Yuan JM (2001)The Shanghai Cohort Study113 MI, and

74 other IHD
IHDMI: RR = 0.43 (0.23-0.81; P = 0.02).

Other IHD: RR = 0.71 (0.32-1.57; P = 0.68).
19) Pietinen P (1997)The ATBC Study635CHDRR = 1.29 (1.01-1.65; P = 0.07).
17) Albert CM (1998)The Physician's Health Study133Sudden deathRR = 0.43 (0.20-0.93; P = 0.21).
15) Järvinen R (2006)The Finnish Mobile Clinic Health Survey335 men, and

163 women
CHDMen: RR = 0.96 (0.68-1.38; P = 1.00).

Women: RR = 0.73 (0.44-1.19; P = 0.31).
13) Hu FB (2002)The Nurses' Health Study484CHDRR = 0.62 (0.44-0.88; P = < 0.001).
13) Ascherio A (1995)The Health Professionals Follow Up Study264CHDRR = 1.03 (0.70-1.52; P = 0.94).
12) Dolecek TA (1992)The Multiple Risk Factor Intervention Trial175CHDRR = 0.61 (P = < 0.05).
7) Streppel MT (2008)The Zutphen Study336CHDHR = 0.65 (0.40-1.06).
Total number of cases: 4,608Average RR = 0.85


Prospective studies of dietary long-chain omega-3 and heart failure risk:
AuthorCohort nameCasesEnd pointRelative Risk (RR)
43) Dijkstra CS (2009)The Rotterdam Study669RiskRR = 0.89 (0.69-1.14; P = 0.27).
42) Levitan EB (2010)The Swedish Mammography Cohort651RiskRR = 0.81 (0.63-1.05).
42) Levitan EB (2009)The Cohort of Swedish Men597 healthy men, and

? men with MI or diabetes
RiskHealthy men: HR = 1.00 (0.77-1.29).

Men with MI or diabetes: HR = 1.30 (0.92-1.83).
39) Yamagishi K (2008)The JACC Study307mortalityHR = 0.80 (0.55-1.17; P = 0.13).
27) Mozaffarian D (2005)The Cardiovascular Health Study955RiskHR = 0.63 (0.57-0.94; P = 0.009).
Total number of cases: 3,179+ XAverage RR = 0.81

Long-chain omega-3 fatty acids and stroke.

Results:
Total stroke: Data was provided by 8 cohorts, including 3,145 cases.
A significant protective effect was found in one cohort including women only (Iso H [13]). No other associations were found. RR's were available from 7 cohorts. The average RR = 0.91.
Ischemic stroke: Data was provided by 3 cohorts, including 1,044 cases.
No associations were found. The average RR = 0.79.
Hemorrhagic stroke: Data was provided by 3 cohorts, including 367 cases.
No associations were found. The average RR = 1.04.
Effect modification:

  • In one cohort, a significant protective effect against ischemic stroke was found only among subjects in the middle tertile of consumption of alpha-linolenic acid (He K [13]).
  • Risk of thrombotic infarction was lower among non-users of aspirin, but only for the highest level of consumption of long-chain omega-3 fatty acids (Iso H [13]).

Subjects with prevalent disease: No data was found.

Conclusion: Few associations were found. No evidence was found for an association between consumption of dietary long-chain omega-3 fatty acids and stroke.

Prospective studies of dietary long-chain omega-3 and total stroke:
AuthorCohort nameCasesEnd pointRelative Risk (RR)
+38) Kaushik S (2008)The Blue Mountains Eye Study69MortalityHR = 0.48 (0.19-2.22).
23) Nagata C (2002)The Takayama Study137 men, and

132 women
MortalityMen: HR = 1.19 (0.78-1.81; P = 0.37).

Women: HR = 0.87 (0.58-1.30; P = 0.49).
22) Folsom AR (2004)The Iowa Women's health Study313MortalityNo significant association.
20) Yuan JM (2001)The Shanghai Cohort Study480MortalityRR = 1.00 (0.75-1.33; P = 0.36).
17) Morris MC (1995)The Physician's Health Study173RiskRR = 1.0 (0.6-1.6; P = 0.49).
15) Montonen J (2009)The Finnish Mobile Clinic Health Examination Survey659RiskRR = 1.01 (0.80-1.28; P = 0.90).
13) He K (2002)The Health Professional's Follow-up Study608RiskRR = 0.87 (0.56-1.37; P = 0.71).
+13) Iso H (2001)The Nurses' Health Study574RiskRR = 0.72 (0.53-0.99; P = 0.12).
Total number of cases: 3,145Average RR = 0.91


Prospective studies of dietary long-chain omega-3 and ischemic stroke:
AuthorCohort nameCasesEnd pointRelative Risk (RR)
15) Montonen J (2009)The Finnish Mobile Clinic Health Examination Survey364RiskRR = 0.91 (0.66-1.26; P = 0.66).
13) He K (2002)The Health Professional's Follow-up Study377RiskRR = 0.73 (0.43-1.25; P = 0.73
+ 13) Iso H (2001)The Nurses' Health Study303Total ischemic stroke riskRR = 0.71 (0.46-1.10; P = 0.28).
Total number of cases: 1,044Average RR = 0.79


Prospective studies of dietary long-chain omega-3 and hemorrhagic stroke:
AuthorCohort nameCasesEnd pointRelative Risk (RR)
15) Montonen J (2009)The Finnish Mobile Clinic Health Examination Survey80RiskRR = 1.56 (0.77-3.15; P = 0.22).
13) He K (2002)The Health Professional's Follow-up Study106RiskRR = 1.14 (0.34-3.84; P = 0.87).
+13) Iso H (2001)The Nurses' Health Study181Total hemorrhagic stroke riskRR = 0.76 (0.43-1.37; P = 0.44).
Total number of cases: 186Average RR = 1.32