Dietary a-Linolenic Acid, Marine x-3 Fatty Acids, and Mortality in a Population With High Fish Consumption: Findings From the PREvencion con DIeta MEDiterranea (PREDIMED) Study Aleix Sala-Vila, DPharm, PhD;* Marta Guasch-Ferre, RD, PhD;* Frank B. Hu, MD, PhD; Ana Sanchez-Tainta, RD; Monica Bullo, BSc, PhD; Merce Serra-Mir, RD; Carmen Lopez-Sabater, DPharm, PhD; Jose V. Sorlı, MD, PhD; Fernando Aros, MD, PhD; Miquel Fiol, MD, PhD; Miguel A. Mu~noz, MD, PhD; Luis Serra-Majem, MD, PhD; J. Alfredo Martınez, DPharm, MD, PhD; Dolores Corella, DPharm, PhD; Montserrat Fito, MD, PhD; Jordi Salas-Salvado, MD, PhD; Miguel A. Martınez-Gonzalez, MD, PhD; Ramon Estruch, MD, PhD; Emilio Ros, MD, PhD; for the PREDIMED Investigators Background-—Epidemiological evidence suggests a cardioprotective role of a-linolenic acid (ALA), a plant-derived x-3 fatty acid. It is unclear whether ALA is beneficial in a background of high marine x-3 fatty acids (long-chain n-3 polyunsaturated fatty acids) intake. In persons at high cardiovascular risk from Spain, a country in which fish consumption is customarily high, we investigated whether meeting the International Society for the Study of Fatty Acids and Lipids recommendation for dietary ALA (0.7% of total energy) at baseline was related to all-cause and cardiovascular disease mortality. We also examined the effect of meeting the society’s recommendation for long-chain n-3 polyunsaturated fatty acids (≥500 mg/day). Methods and Results-—We longitudinally evaluated 7202 participants in the PREvencion con DIeta MEDiterranea (PREDIMED) trial. Multivariable-adjusted Cox regressionmodels were fitted to estimate hazard ratios. ALA intake correlated towalnut consumption (r=0.94). During a 5.9-y follow-up, 431 deaths occurred (104 cardiovascular disease, 55 coronary heart disease, 32 sudden cardiac death, 25 stroke). The hazard ratios formeeting ALArecommendation (n=1615, 22.4%) were 0.72 (95% CI 0.56–0.92) for all causemortality and 0.95 (95% CI 0.58–1.57) for fatal cardiovascular disease. The hazard ratios formeeting the recommendation for long-chain n-3 polyunsaturated fatty acids (n=5452, 75.7%) were 0.84 (95% CI 0.67–1.05) for all-causemortality, 0.61 (95% CI 0.39–0.96) for fatal cardiovascular disease, 0.54 (95% CI 0.29–0.99) for fatal coronary heart disease, and 0.49 (95% CI 0.22–1.01) for sudden cardiac death. The highest reduction in all-cause mortality occurred in participants meeting both recommendations (hazard ratio 0.63 [95% CI 0.45–0.87]). Conclusions-—In participants without prior cardiovascular disease and high fish consumption, dietary ALA, supplied mainly by walnuts and olive oil, relates inversely to all-cause mortality, whereas protection from cardiac mortality is limited to fish-derived long-chain n-3 polyunsaturated fatty acids. Clinical Trial Registration-—URL: http://www.Controlled-trials.com/. Unique identifier: ISRCTN35739639. ( J Am Heart Assoc.2016;5:e002543 doi: 10.1161/JAHA.115.002543)
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