Omega-3 Fatty Acids and Coronary Heart Disease: Clinical and Mechanistic Perspectives

Background

Dr. William S. Harris and colleagues published this comprehensive review in Atherosclerosis (PMID: 18160071), examining the clinical and mechanistic evidence for omega-3 fatty acids in coronary heart disease prevention.

Study Design

Narrative review synthesizing evidence from epidemiological studies, randomized trials, and mechanistic research on EPA and DHA effects on cardiovascular outcomes.

Key Findings

Multiple cardioprotective mechanisms:

Mechanism	Effect	Clinical Impact
Triglyceride lowering	−25-30% at 3-4 g/day	Reduces atherogenic particles
Anti-arrhythmic	Membrane stabilization	Prevents sudden death
Anti-inflammatory	Reduces IL-6, TNF-α, CRP	Plaque stabilization
Anti-thrombotic	Reduces platelet aggregation	Prevents acute events
Endothelial function	Improves NO availability	Vasodilation
Blood pressure	Modest reduction (2-4 mmHg)	Cardiovascular protection

Evidence from major trials:

• •GISSI-Prevenzione: 45% reduction in sudden death
• •JELIS: 19% reduction in major coronary events
• •Consistent benefit across populations

Mechanistic Insights

Omega-3s integrate into cell membranes throughout the body, affecting:

• •Ion channel function (heart rhythm)
• •Eicosanoid balance (inflammation)
• •Gene expression (lipid metabolism)
• •Membrane fluidity (receptor function)

Clinical Implications

Omega-3 supplementation (1-4 g/day) is appropriate for:

• •Post-MI secondary prevention
• •Hypertriglyceridemia
• •General cardiovascular risk reduction

Higher doses needed for triglyceride lowering than for anti-arrhythmic effects.

Metabolic Health Perspective

Omega-3s address multiple components of metabolic syndrome simultaneously. The Omega-3 Index provides a way to verify adequate tissue levels, targeting ≥8% for optimal benefit.