Erythrocyte n-6 Fatty Acids and Risk for Cardiovascular Outcomes and Total Mortality in the Framingham Heart Study

Abstract

Background: The prognostic value of erythrocyte levels of n-6 fatty acids (FAs) for total mortality and cardiovascular disease (CVD) outcomes remains an open question. Methods: We examined cardiovascular (CV) outcomes and death in 2500 individuals in the Framingham Heart Study Offspring cohort without prevalent CVD (mean age 66 years, 57% women) as a function of baseline levels of different length n-6 FAs (18 carbon, 20 carbon, and 22 carbon) in the erythrocyte membranes. Clinical outcomes were monitored for up to 9.5 years (median follow up, 7.26 years). Cox proportional hazards models were adjusted for a variety of demographic characteristics, clinical status, and red blood cell (RBC) n-6 and long chain n-3 FA content. Results: There were 245 CV events, 119 coronary heart disease (CHD) events, 105 ischemic strokes, 58 CVD deaths, and 350 deaths from all causes. Few associations between either mortality or CVD outcomes were observed for n-6 FAs, with those that were observed becoming non-significant after adjusting for n-3 FA levels. Conclusions: Higher circulating levels of marine n-3 FA levels are associated with reduced risk for incident CVD and ischemic stroke and for death from CHD and all-causes; however, in the same sample little evidence exists for association with n-6 FAs. Further work is needed to identify a full profile of FAs associated with cardiovascular risk and mortality.

Association between Plasma N-6 Polyunsaturated Fatty Acids Levels and the Risk of Cardiovascular Disease in a Community-based Cohort Study

“…A systematic review reported that N-3 and N-6 PUFAs have competing roles in the production of anti-inflammatory and inflammatory eicosanoids 21 . Some studies have suggested that the EPA:AA ratio was associated with CHD risk, but they could not find a consistent conclusion regarding the same 34 .…”

“…The clinical value of N-6 PUFAs for total mortality and CVD risks remains controversial 21,34 . In the Framingham Heart Study, higher marine N-3 PUFA concentrations were related to reduced CVD, ischaemic stroke, and mortality risks.…”

Fatty Acid Profile and Desaturase Activities in 7–10-Year-Old Children Attending Primary School in Verona South District: Association between Palmitoleic Acid, SCD-16, Indices of Adiposity, and Blood Pressure

“…The cardiovascular effects of omega-6 FA are still controversial, with some studies and meta-analysis indicating a protective effect of linoleic acid (LA), and possibly of arachidonic acid (AA), on incident CV disease [4] and other studies reporting no or a possible harmful association of omega-6 FA with CV events [16,17]. Our previous study was in line with the hypothesis of a possible beneficial effect of arachidonic acid on CV risk factors and non-alcoholic fatty liver disease [3].…”

Erythrocyte n-6 Fatty Acids and Risk for Cardiovascular Outcomes and Total Mortality in the Framingham Heart Study

“…Accordingly, ratios like n-6:n-3 18 or AA:EPA 19 have been promoted as better summary metrics of PUFA status than either family alone. This perspective has, however, been criticized on both theoretical [20][21][22][23] and evidential [24][25][26] bases.…”

“…The Framingham Heart Study is a longitudinal community-based cohort study that was initiated in 1948. The selection criteria for the Framingham Offspring Cohort and the Framingham Omni Cohort have previously been described 4,5 (http://nhlbi.nih.gov/about/framingham). Briefly, adult children of the Original cohort were recruited in 1971 into the Framingham Offspring Cohort.…”