Abstract
Objectives
Previous studies have suggested that polyunsaturated fatty acids (PUFAs) levels may be inversely associated with metabolism syndrome (MS) and atherosclerosis (AS). And yet, null results from recent long-term randomized clinical trials and meta-analysis threw an uncertainty to the cardioprotective benefits of n-3 and n-6 PUFAs. We prospectively examined the associations between erythrocyte PUFAs levels and MS and carotid AS and the intermediary effects of retinol-binding protein 4 (RBP4).
Methods
This prospective study recruited 4040 participants (40-75 years old) in 2008–2013. Follow-up examinations were performed every 3 years. We assessed erythrocyte PUFAs proportion at baseline and determined serum RBP4 at the first follow-up. The carotid intima-media thickness (IMT) at the common carotid artery (CCA) and bifurcation of the carotid artery (BIF) were measured by B-mode ultrasound at baseline and the first follow-up.
Results
A total of 2745 participants were included in the analysis. The multivariable adjusted hazards ratios (HRs) [95% confidence interval (CI)] of incidence of MS for the top (vs. lowest) tertile of erythrocyte PUFA were 0.71 (0.59, 0.86) (docosahexaenoic acid, DHA), 0.78 (0.65, 0.95) (docosapentaenoic acid, DPA) for n-3 PUFAs and 0.57 (0.47, 0.69) (arachidonic acid, ARA) and 0.75 (0.62, 0.91) (dodecylthioacetic acid, DTA) for n-6 PUFAs (all Ps trend < 0.05) during the 5.4-year follow-up. Similarly, erythrocyte DPA and DHA, ARA, DTA were significantly inversely and dose-dependently associated with incidence of carotid AS (Ptrend < 0.001 to 0.033). While a positive association of gamma-linolenic acid (GLA) was found with both incidence of MS and carotid AS. Pathway analyses indicated DHA and ARA to MS and AS associations were mediated by lowering serum RBP4, which were positively associated with MS and AS risk.
Conclusions
Higher erythrocyte DPA, DHA (n-3 PUFA) and ARA, DTA (n-6 PUFA) but lower GLA were associated with incidence of MS and AS. Inverse association linking DHA, LA and ARA to incidence of MS and AS was mediated by reducing serum RBP4. Potential differences in the cardiovascular disease effects of different types of circulating PUFAs were suggested.
Funding Sources
This study was jointly supported by the National Natural Science Foundation of China (No. 81472965, 81730090, 81773416) and the 5010 Program for Clinical Researches (No. 2007032) by the Sun Yat-sen University, Guangzhou, P. R. China. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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