Associations between n-3 and n-6 polyunsaturated fatty acids and stroke risk, mediated by the dietary inflammatory...

This study aimed to explore the associations between polyunsaturated fatty acids (PUFAs), inflammatory biomarkers, and stroke risk, and to assess the mediating role of the dietary inflammatory index (DII).

Data from 26,556 participants in National Health and Nutrition Examination Survey (NHANES) 2007-2018 were analyzed. Weighted logistic regression models were used to examine the relationships between n-3 PUFAs, n-6 PUFAs, inflammatory biomarkers, and stroke risk. Propensity score matching (PSM) was applied to match stroke and non-stroke participants in a 1:2 ratio. Restricted cubic spline (RCS) analysis assessed non-linear associations between PUFAs, DII, and stroke risk, and mediation analysis explored the role of DII in the PUFAs-stroke relationship. Subgroup analyses were conducted to assess effect modification by demographic and clinical variables.

Of the 26,556 participants, 1,022 (3.85%) reported a stroke diagnosis. PSM was conducted to generate a balanced cohort of 1,021 stroke cases and 2,040 non-stroke controls. Before PSM, higher intake (Q3 and Q4) of n-3 and n-6 PUFAs was significantly inversely correlated with stroke risk. After PSM, in the fully adjusted model, the fourth quartiles of n-3 and n-6 PUFAs remained negatively associated with stroke, with ORs of 0.72 (95%CI: 0.53-0.97, P for trend = 0.001) and 0.63 (95%CI: 0.47-0.86, P for trend < 0.001), respectively. Conversely, the highest quartile of DII and neutrophil-to-high-density lipoprotein cholesterol ratio (NHR) remained positively associated with stroke, with an OR of 1.66 (95%CI: 1.24-2.24, P for trend < 0.001) and 1.46 (95%CI: 1.07-2.00, P for trend = 0.002). Stroke risk gradually decreased alongside elevated n-3 PUFA concentrations below the threshold values of 34.44 mg/kg/day (pre-PSM) and 35.71 mg/kg/day (post-PSM), and trended upward when exceeding these critical levels. Mediation analysis suggested DII significantly mediated the effects of n-3 PUFAs (P = 0.02) and n-6 PUFAs (P < 0.01) on stroke after PSM. A significant interaction was observed between n-6 PUFAs and poverty income ratio (PIR) (P for interaction = 0.006).

The Q4 of both n-3 and n-6 PUFAs are inversely associated with stroke risk. The nonlinear, biphasic relationship observed between n-3 PUFAs intake and stroke risk. DII's mediating role underscores the importance of dietary inflammation in managing stroke risk.