Plasma n-3 polyunsaturated fatty acids in chronic heart failure in the GISSI-Heart Failure Trial: relation with fish intake, circulating biomarkers, and mortality.
Treatment with long-chain n-3 polyunsaturated fatty acids (n-3 PUFAs) can improve clinical outcomes in patients with heart failure (HF). Circulating levels of n-3 PUFA, an objective estimation of exposure, have never been measured in a large cohort of patients with HF.


METHODS
We measured n-3 PUFA in plasma phospholipids at baseline and after 3 months in 1,203 patients with chronic HF enrolled in the GISSI-Heart Failure trial and randomized to n-3 PUFA 1 g/daily or placebo. N-3 PUFA levels were related to clinical characteristics, pharmacologic treatments, dietary habits, circulating biomarkers, and mortality.


RESULTS
Baseline n-3 PUFA (5.1 ± 1.8 mol%) was associated with dietary fish intake, with an average difference of 43% between patients with the lowest and highest consumptions (P < .0001). Baseline eicosapentaenoic acid (EPA) but not docosahexaenoic acid (DHA) was inversely related to C-reactive protein, pentraxin-3, adiponectin, natriuretic peptide, and troponin levels. Three-month treatment with n-3 PUFA raised their levels by 43%, independently of dietary fish consumption; increases in EPA levels were associated with decreased pentraxin-3. Low baseline levels of EPA but not DHA were no longer related to higher mortality after the addition of circulating biomarkers to multivariable models.


CONCLUSIONS
Before supplementation, circulating n-3 PUFA levels in patients with chronic HF mainly depend on dietary fish consumption and are inversely related to inflammatory markers and disease severity. Three-month treatment with n-3 PUFA markedly enriched circulating EPA and DHA, independently of fish intake, and lowered pentraxin-3. Low EPA levels are inversely related to total mortality in patients with chronic HF.
Department of Cardiovascular Research, Istituto di Ricerche Farmacologiche "Mario Negri," Milan, Italy.
Serge
S
Masson
Roberto
R
Marchioli
Dariush
D
Mozaffarian
Roberto
R
Bernasconi
Valentina
V
Milani
Luana
L
Dragani
Mariateresa
M
Tacconi
Rosa Maria
RM
Marfisi
Luisa
L
Borgese
Vincenzo
V
Cirrincione
Oreste
O
Febo
Enrico
E
Nicolis
Aldo P
AP
Maggioni
Gianni
G
Tognoni
Luigi
L
Tavazzi
Roberto
R
Latini
D000368:Aged; D015415:Biomarkers / Q000097:blood; D019587:Dietary Supplements; D004311:Double-Blind Method; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D005260:Female; D005395:Fish Oils / Q000008:administration & dosage*; D005500:Follow-Up Studies; D006333:Heart Failure / Q000097:blood* / Q000178:diet therapy / Q000401:mortality; D006801:Humans; D007558:Italy / Q000453:epidemiology; D008297:Male; D011446:Prospective Studies; D015996:Survival Rate / Q000639:trends
D015415:Biomarkers; D015525:Fatty Acids, Omega-3; D005395:Fish Oils