Omega-3 Fatty Acids and Cardiovascular Disease: Effects on Risk Factors and Clinical Events

Background

Drs. Dariush Mozaffarian (Harvard School of Public Health) and Jason Wu published this comprehensive review in the Journal of the American College of Cardiology (PMID: 22051327), synthesizing evidence on omega-3 effects on cardiovascular outcomes.

Study Design

Systematic review examining omega-3 fatty acid effects on cardiovascular risk factors, molecular pathways, and clinical endpoints.

Key Findings

Dose-response relationships:

Effect	Effective Dose
Sudden cardiac death reduction	250 mg/day EPA+DHA
Triglyceride lowering	2-4 g/day
Heart rate reduction	≥1 g/day (−1.6 bpm)
Blood pressure reduction	≥3 g/day (−1.5/−1.0 mmHg)

Clinical outcomes from major trials:

Outcome	Risk Reduction
Sudden cardiac death	45-50%
CHD death	15-20%
All-cause mortality	10-15%

Minimal effective dose: 250-500 mg/day EPA+DHA for mortality reduction

Mechanistic Insights

Cardioprotective mechanisms:

1. •Anti-arrhythmic: Membrane stabilization prevents fatal arrhythmias
2. •Triglyceride reduction: Decreases VLDL production, enhances clearance
3. •Anti-inflammatory: Reduces cytokines, produces resolvins
4. •Anti-thrombotic: Reduces platelet aggregation
5. •Vascular: Improves endothelial function

Clinical Implications

Even modest omega-3 intake (1-2 fish servings/week ≈ 250 mg/day EPA+DHA) reduces cardiovascular mortality. Higher doses needed for triglyceride management.

Metabolic Health Perspective

Omega-3s address multiple metabolic syndrome components simultaneously. For metabolic optimization, the Omega-3 Index target of ≥8% ensures tissue saturation for cardioprotective benefits.