EC Tore1, AM Briones2, RM Bruno3, J Dalli4, SJPM Eussen5, CG Schalkwijk1, MMJ van Greevenbroek1
1Internal Medicine department, CARIM Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, Netherlands; 2Pharmacology department, Universidad Autónoma de Madrid, Hospital La Paz Institute for Health Research, Madrid, CiberCV, Spain; 3Pharmacology Unit, Assistance Publique-Hôpitaux de Paris, Paris, France; 4William Harvey Research Institute, Queen Mary University of London, London, UK; 5Epidemiology department, CAPHRI Care and Public Health Research Institute and CARIM Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, Netherlands
e.tore@maastrichtuniversity.nl
Background: Research suggests that n-3 polyunsaturated fatty acids (PUFAs) may lower cardiovascular disease (CVD) risk, potentially by reducing low-grade inflammation (LGI). We examined whether LGI mediates the association between n-3 PUFA concentrations and CVD, and if this is modified by type 2 diabetes (T2D).
Methods: Cross-sectional data (n=3158, 50.9% men, 60±8y, 26.6% T2D) were analyzed. Total n-3 PUFAs and DHA were measured in fasted EDTA plasma with 1H NMR. LGI was defined as the average z-score of plasma inflammation biomarkers (CRP, SAA, IL-6, IL-8, sICAM-1, TNF-α). CVD was self-reported as a history of coronary heart disease, cerebrovascular disease, or peripheral artery disease (n=225 with T2D, n=292 without). Mediation analyses assessed whether LGI (potential mediator) explained (part of) the associations between n-3 PUFAs (main exposures, z-standardized) and CVD (binary outcome). Analyses were adjusted for relevant confounders and stratified by T2D. Statistical significance was set at p<0.05.
Results: Total n-3 PUFAs was inversely associated with CVD in participants with and without T2D (non-T2D: OR=0.68[0.58,0.79], T2D: OR=0.69[0.57,0.84]). The association with LGI in participants without T2D was inverse (β=-0.11[-0.15,-0.07]). In participants with T2D, these associations were weaker and non-significant (NS). Positive associations between LGI and CVD, on the other hand, were stronger in T2D (OR=1.21[1.02,1.45]), while they were positive but NS in the non-T2D group (OR=1.08[0.95,1.25]). No significant mediation effect by LGI were observed in either group. All results were similar for DHA.
Discussion/Conclusion: Plasma-based LGI did not explain a substantial part of the inverse associations between n-3 PUFAs and CVD in participants with or without T2D. However, the associations of n-3 PUFAs with CVD were weaker in those with T2D, suggesting that the underlying pathway may be altered in T2D. Further research is needed to explain the effect of n-3 PUFAs on CVD, and the roles of LGI and T2D therein.