Polyunsaturated Fat Intake Estimated by Circulating Biomarkers and Risk of Cardiovascular Disease and All-Cause Mortality in a Population-Based Cohort of 60-Year-Old Men and Women

Abstract

Background-High intake of polyunsaturated fatty acids (PUFAs) may reduce the risk of cardiovascular disease (CVD) and mortality. Large, prospective studies including both sexes and circulating PUFAs as dietary biomarkers are needed. We investigated sex-specific associations of the major dietary PUFAs, eicosapentaenoic acid, docohexaenoic acid, linoleic acid, and α-linolenic acid, with incident CVD and all-cause mortality in a population-based cohort. Methods and Results-PUFAs in serum cholesterol esters were measured at baseline in 60-year-old Swedish women (n=2193) and men (n=2039). With the use of national registers, 484 incident CVD events (294 men and 190 women) and 456 all-cause deaths (265 men and 191 women) were identified during follow-up (median, 14.5 years) in individuals without prior CVD at baseline. Associations of PUFAs with CVD and mortality were evaluated with Cox proportional hazard models. In multivariable-adjusted models, 1-SD increases in eicosapentaenoic acid and docohexaenoic acid were associated with lower risk of incident CVD among women (hazard ratio PUFAs seem to have selective roles in the development of CVD, whereas possible influences on non-CVD outcomes are less clear. 9 Dietary intake of EPA, DHA, LA, and, to a lesser extent, ALA is reflected in the FA composition in serum cholesteryl esters (CEs); thus, the proportions of these PUFAs in CEs can be used as biomarkers to assess the intake of the respective PUFA.[10-12 Accordingly, FA composition (especially EPA, DHA, and LA) in CEs correlates well with self-reported FA intake in both Swedish 13 and other cohorts.14 Several prospective cohort and nested case-control studies have used serum CE FAs as a biomarker of dietary fat and investigated possible relationships with risks of all-cause and CVD mortality, 15 fatal coronary heart disease (CHD), 16 and incidences of CHD, 17 heart failure, 18 and stroke. 19,20 Among middle-aged Swedish men, a 1-SD increase (5.2%) in serum CE LA was associated with 13% and 15% lower risk of all-cause and CVD mortality, respectively, whereas no significant associations were observed for serum CE EPA, DHA, or ALA. In addition, a recent meta-analysis suggested that CE LA is associated with a lower risk of fatal CHD, whereas no such associations have been observed for n-3 PUFAs. 16 However, previous studies investigating relationships between serum CE PUFAs and CVD-related outcomes have included predominantly men, although men and women may differ in CVD risks and mortality. 21 Thus, identification of possible sex-specific associations might have been hampered by the limited number of women.Furthermore, recent studies have reported inverse associations of both n-6 and n-3 PUFAs in plasma phospholipid with all-cause and cause-specific mortality and with incident CVD in a US cohort of older men and women. 22,23 This study investigated associations between biomarkers of PUFA intake (EPA, DHA, LA, and ALA) in serum CEs and incident CVD and all-cause mortality in men and women, separately and combined, in a ...

Red blood cell polyunsaturated fatty acids and mortality in the Women's Health Initiative Memory Study

“…in heart failure 27 ), our observations can be considered supportive of a beneficial association between DPAn-3 and total mortality. Our null findings for ALA agree with some previous studies 8, 14 , but ALA levels have been associated with CVD death 26 , and ALA intake was associated with reduced total mortality in a large RCT from Spain 28 .…”

“…For example, LA – which is a major driver of the n-6:n-3 ratio – is not in the PUFA Factor score, and this may have contributed to the superior predictive power of this metric. The reason for this may be that LA is actually protective (based on the findings of 4 previous studies 7–9, 14 ; it was neutral in the present study), not harmful; and to include a “protective” FA in with other “harmful” FAs in the same term (total n-6) adds unnecessary noise and obscures the signal. The fact that the simpler ARA/EPA metric had similar predictive power as the n6:n3 ratio despite its non-inclusion of LA, suggests that the other FAs in the Factor score that are not present in this simple ratio (e.g., DHA, and the longer-chain products of ARA) appear to contribute to its improved predictive value.…”

Plasma n-6 Fatty Acid Levels Are Associated With CD4 Cell Counts, Hospitalization, and Mortality in HIV-Infected Patients

“…Previous studies on the long-term effects plasma n6-fatty acids on death were done in patients not known to be HIV-infected and showed that higher linoleic acid levels, but not other n6-fatty acids, were associated with a reduced risk of all-cause mortality. 21,22 These studies are consistent with short-term or cross-sectional studies showing inverse associations between n6-fatty acids and the metabolic syndrome or its components in HIV-uninfected individuals. 23 Studies on effects of n6-fatty acids on outcomes of HIV-infection have been conducted either in vitro or have focused on short-term clinical measures such as inflammation or pregnancy outcomes in HIV-infected patients.…”

“…Although there are no epidemiologic studies investigating the direct effect of n6-fatty acids on medium- and long-term clinical outcomes in HIV/AIDS patients, studies from elderly non-HIV participants (>65 years) in the US 21 and Sweden (age>60 years) 22 show that higher plasma levels of linoleic acid, but not gamma-linolenic acid or dihomo-gamma-linolenic acid or arachidonic acid, are inversely associated with reduced risk of all-cause mortality, in part supporting the inverse association observed for linoleic acid in our study. Another study that pooled 83,349 women from the Nurses’ Health Study and 42,884 men from the Health Professionals Follow-up Study also showed that total n6-PUFA, linoleic acid and arachidonic acid estimated from food frequency questionnaires were associated with a 10-15% lower risk of all-cause mortality.…”

Misvisende om kosthold i ny nasjonal retningslinje for forebygging av hjerte- og karsykdommer

“…Nyere biomarkør-studier støtter at et høyere inntak av flerumettet fett er forbundet med lavere risiko for koronar hjertesykdom [244][245][246][247] . Slike funn er imidlertid vanskelig å tolke og kan ikke «oversettes» til kvantitative råd om inntak ettersom studiene måler andeler av fettsyrer i vev.…”