Dietary and Circulating Long-Chain Omega-3 Polyunsaturated Fatty Acids and Mortality Risk After Myocardial Infarction: A Long-Term Follow-Up of the Alpha Omega Cohort

Kamalita Pertiwi, Leanne K Küpers, Janette de Goede, Peter L Zock, Daan Kromhout, Johanna M Geleijnse, Kamalita Pertiwi, Leanne K Küpers, Janette de Goede, Peter L Zock, Daan Kromhout, Johanna M Geleijnse

Abstract

Background Habitual intake of long-chain omega-3 fatty acids, especially eicosapentaenoic and docosahexaenoic acid (EPA+DHA) from fish, has been associated with a lower risk of fatal coronary heart disease (CHD) in population-based studies. Whether that is also the case for patients with CHD is not yet clear. We studied the associations of dietary and circulating EPA+DHA and alpha-linolenic acid, a plant-derived omega-3 fatty acids, with long-term mortality risk after myocardial infarction. Methods and Results We analyzed data from 4067 Dutch patients with prior myocardial infarction aged 60 to 80 years (79% men, 86% on statins) enrolled in the Alpha Omega Cohort from 2002 to 2006 (baseline) and followed through 2018. Baseline intake of fish and omega-3 fatty acids were assessed through a validated 203-item food frequency questionnaire and circulating omega-3 fatty acids were assessed in plasma cholesteryl esters. Hazard ratios (HRs) with 95% CIs were obtained from Cox regression analyses. During a median follow-up period of 12 years, 1877 deaths occurred, of which 515 were from CHD and 834 from cardiovascular diseases. Dietary intake of EPA+DHA was significantly inversely associated with only CHD mortality (HR, 0.69 [0.52-0.90] for >200 versus ≤50 mg/d; HR, 0.92 [0.86-0.98] per 100 mg/d). Similar results were obtained for fish consumption (HRCHD, 0.74 [0.53-1.03] for >40 versus ≤5 g/d; Ptrend: 0.031). Circulating EPA+DHA was inversely associated with CHD mortality (HR, 0.71 [0.53-0.94] for >2.52% versus ≤1.29%; 0.85 [0.77-0.95] per 1-SD) and also with cardiovascular diseases and all-cause mortality. Dietary and circulating alpha-linolenic acid were not significantly associated with mortality end points. Conclusions In a cohort of Dutch patients with prior myocardial infarction, higher dietary and circulating EPA+DHA and fish intake were consistently associated with a lower CHD mortality risk. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03192410.

Keywords: coronary heart disease; mortality; myocardial infarction; omega‐3 fatty acids; plasma fatty acids; prospective cohort study.

Figures

Figure 1. Associations of ( A )…
Figure 1. Associations of (A) dietary and (B) circulating eicosapentaenoic acid+docosahexaenoic acid (EPA+DHA) with coronary heart disease mortality in 4067 patients with post‐myocardial infarction.
Solid lines are risk estimates evaluated by restricted cubic splines from Cox models showing the shape of the associations on a continuous scale with 5 knots located at 5th, 27.5th, 50th, 72.5th, and 95th percentiles. The y‐axis shows the multivariable‐adjusted hazard ratios for coronary heart disease mortality risk for any dietary or circulating EPA+DHA value, compared with the reference value set at the 5th percentile of dietary (7.8 mg/d) or circulating EPA+DHA (0.99% total fatty acids). Gray areas indicated 95% CIs. One SD of circulating EPA+DHA was 0.95% of total fatty acids. Histograms depict the distributions of dietary or circulating EPA+DHA in the Alpha Omega Cohort. DHA indicates docosahexaenoic acid; EPA, eicosapentaenoic acid; FA, fatty acid; and HR, hazard ratio.
Figure 2. Associations of ( A )…
Figure 2. Associations of (A) dietary and (B) circulating alpha‐linolenic acid (ALA) with coronary heart disease mortality in 4067 patients with post‐myocardial infarction.
Solid lines are risk estimates evaluated by restricted cubic splines from Cox models showing the shape of the associations on a continuous scale with 5 knots located at 5th, 27.5th, 50th, 72.5th, and 95th percentiles. The y‐axis shows the multivariable‐adjusted hazard ratios for coronary heart disease mortality risk for any dietary or circulating ALA value, compared with the reference values set at fifth percentile of dietary (0.49 g/d) or circulating ALA (0.30% of total fatty acids). Gray areas indicated 95% CIs. One SD of circulating ALA was 0.14% of total fatty acids. Histograms depict the distributions of dietary or circulating ALA in the Alpha Omega Cohort. ALA indicates alpha‐linolenic acid; and FA, fatty acids.

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