Dietary α‐Linolenic Acid, Marine ω‐3 Fatty Acids, and Mortality in a Population With High Fish Consumption: Findings From the PREvención con DIeta MEDiterránea (PREDIMED) Study

Background: Epidemiological evidence suggests a cardioprotective role of α‐linolenic acid (ALA), a plant‐derived ω‐3 fatty acid. It is unclear whether ALA is beneficial in a background of high marine ω‐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 PREvención con DIeta MEDiterránea (PREDIMED) trial. Multivariable‐adjusted Cox regression models were fitted to estimate hazard ratios. ALA intake correlated to walnut 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 for meeting ALA recommendation (n=1615, 22.4%) were 0.72 (95% CI 0.56–0.92) for all‐cause mortality and 0.95 (95% CI 0.58–1.57) for fatal cardiovascular disease. The hazard ratios for meeting 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‐cause mortality, 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

PLZF-RAR(alpha), NPM1-RAR(alpha), and other acute promyelocytic leukemia variants: the PETHEMA registry experience and systematic literature review

It has been suggested that 1-2% of acute promyelocytic leukemia (APL) patients present variant rearrangements of retinoic acid receptor alpha (RAR alpha) fusion gene, with the promyelocytic leukaemia zinc finger (PLZF)/RAR(alpha) being the most frequent. Resistance to all-trans-retinoic acid (ATRA) and arsenic trioxide (ATO) has been suggested in PLZF/RAR(alpha) and other variant APLs. Herein, we analyze the incidence, characteristics, and outcomes of variant APLs reported to the multinational PETHEMA (Programa para el Tratamiento de Hemopatias Malignas) registry, and we perform a systematic review in order to shed light on strategies to improve management of these extremely rare diseases. Of 2895 patients with genetically confirmed APL in the PETHEMA registry, 11 had variant APL (0.4%) (9 PLZF-RAR(alpha) and 2 NPM1-RAR(alpha)), 9 were men, with median age of 44.6 years (3 months to 76 years), median leucocytes (WBC) 16.8 x 10(9)/L, and frequent coagulopathy. Eight patients were treated with ATRA plus chemotherapy-based regimens, and 3 with chemotherapy-based. As compared to previous reports, complete remission and survival was slightly better in our cohort, with 73% complete remission (CR) and 73% survival despite a high relapse rate (43%). After analyzing our series and performing a comprehensive and critical review of the literature, strong recommendations on appropriate management of variant APL are not possible due to the low number and heterogeneity of patients reported so far

Masses and compositions of three small planets orbiting the nearby M dwarf L231-32 (TOI-270) and the M dwarf radius valley

We report on precise Doppler measurements of L231-32 (TOI-270), a nearby M dwarf (d = 22 pc, M⋆ = 0.39 M⊙, R⋆ = 0.38 R⊙), which hosts three transiting planets that were recently discovered using data from the Transiting Exoplanet Survey Satellite (TESS). The three planets are 1.2, 2.4, and 2.1 times the size of Earth and have orbital periods of 3.4, 5.7, and 11.4 d. We obtained 29 high-resolution optical spectra with the newly commissioned Echelle Spectrograph for Rocky Exoplanet and Stable Spectroscopic Observations (ESPRESSO) and 58 spectra using the High Accuracy Radial velocity Planet Searcher (HARPS). From these observations, we find the masses of the planets to be 1.58 ± 0.26, 6.15 ± 0.37, and 4.78 ± 0.43 M⊕, respectively. The combination of radius and mass measurements suggests that the innermost planet has a rocky composition similar to that of Earth, while the outer two planets have lower densities. Thus, the inner planet and the outer planets are on opposite sides of the ‘radius valley’ – a region in the radius-period diagram with relatively few members – which has been interpreted as a consequence of atmospheric photoevaporation. We place these findings into the context of other small close-in planets orbiting M dwarf stars, and use support vector machines to determine the location and slope of the M dwarf (Teff < 4000 K) radius valley as a function of orbital period. We compare the location of the M dwarf radius valley to the radius valley observed for FGK stars, and find that its location is a good match to photoevaporation and core-powered mass-loss models. Finally, we show that planets below the M dwarf radius valley have compositions consistent with stripped rocky cores, whereas most planets above have a lower density consistent with the presence of a H-He atmosphere

Prediction of Cardiovascular Disease by the Framingham‐REGICOR Equation in the High‐Risk PREDIMED Cohort: Impact of the Mediterranean Diet Across Different Risk Strata

Background: The usefulness of cardiovascular disease (CVD) predictive equations in different populations is debatable. We assessed the efficacy of the Framingham‐REGICOR scale, validated for the Spanish population, to identify future CVD in participants, who were predefined as being at high‐risk in the PREvención con DIeta MEDiterránea (PREDIMED) study—a nutrition‐intervention primary prevention trial—and the impact of adherence to the Mediterranean diet on CVD across risk categories. Methods and Results: In a post hoc analysis, we assessed the CVD predictive value of baseline estimated risk in 5966 PREDIMED participants (aged 55–74 years, 57% women; 48% with type 2 diabetes mellitus). Major CVD events, the primary PREDIMED end point, were an aggregate of myocardial infarction, stroke, and cardiovascular death. Multivariate‐adjusted Cox regression was used to calculate hazard ratios for major CVD events and effect modification from the Mediterranean diet intervention across risk strata (low, moderate, high, very high). The Framingham‐REGICOR classification of PREDIMED participants was 25.1% low risk, 44.5% moderate risk, and 30.4% high or very high risk. During 6‐year follow‐up, 188 major CVD events occurred. Hazard ratios for major CVD events increased in parallel with estimated risk (2.68, 4.24, and 6.60 for moderate, high, and very high risk), particularly in men (7.60, 13.16, and 15.85, respectively, versus 2.16, 2.28, and 3.51, respectively, in women). Yet among those with low or moderate risk, 32.2% and 74.3% of major CVD events occurred in men and women, respectively. Mediterranean diet adherence was associated with CVD risk reduction regardless of risk strata (P>0.4 for interaction). Conclusions: Incident CVD increased in parallel with estimated risk in the PREDIMED cohort, but most events occurred in non–high‐risk categories, particularly in women. Until predictive tools are improved, promotion of the Mediterranean diet might be useful to reduce CVD independent of baseline risk

Dietary α-linolenic acid, marine ω-3 fatty acids, and mortality in a population with high fish consumption: Findings from the PREvención con DIeta MEDiterránea (PREDIMED) Study

12 Páginas.-- 6 Tablas.-- 1 FiguraBackground-Epidemiological evidence suggests a cardioprotective role of α-linolenic acid (ALA), a plant-derived ω-3 fatty acid. It is unclear whether ALA is beneficial in a background of high marine ω-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 PREvención con DIeta MEDiterránea (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.This study was funded in part by Instituto de Salud Carlos III (ISCIII) (Spanish Ministry of Economy) through grants RTIC G03/140, RTIC RD 06/0045, Centro Nacional de Investigaciones Cardiovasculares CNIC 06/2007, ISCIII FIS PS09/01292, the Spanish Ministry of Science and Innovation (MICINN) AGL2010‐22319‐C03‐02 and AGL2009‐13906‐C02‐02, and an unrestricted grant from the California Walnut Commission. Sala‐Vila holds a Miguel Servet I fellowship from the Ministry of Economy and Competitiveness through the ISCIII