Tore EC1, Briones AM2, Bruno RM3, Dalli J4, van Greevenbroek MMJ1
1CARIM Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, the Netherlands. 2Universidad Autónoma de Madrid, Hospital La Paz Institute for Health Research, Madrid, CiberCV, Spain. 3INSERM U970, Paris Cardiovascular Research Centre—PARCC, Université Paris Cité, 56 Rue Leblanc, Paris 75015, France. 4William Harvey Research Institute, Queen Mary University of London, London, United Kingdom.
Background: Specialized pro-resolving mediators (SPMs; Lipoxins, Resolvins, Protectins, and Maresins) are bioactive compounds derived from omega-6s and omega-3s involved in inflammation resolution. Limited preclinical and human evidence suggests they may reduce myocardial infarction (MI) risk. We examined whether SPMs are associated with incident MI in a population-based cohort.
Methods: Data from a case-control subset of The Maastricht Study were analyzed (noT2DM: n=282, 31% female, 63yrs [58,67]; T2DM: n=144, 26% female, 65yrs [61,68]). Cases were selected from participants who experienced at least one MI event at follow-up, according to hospital records or yearly questionnaires. Controls were selected among participants without cardiovascular events, and 1:1 matched on age (±5yrs), sex (male/female), education (low/middle/high) and enrollment date (±24mo). Baseline SPM concentrations were measured in fasting EDTA plasma by LC-MS/MS. Concentrations below the detection limit were imputed with a value=1/5 of the lowest measured value for the corresponding SPM. SPMs belonging to the same families were grouped into standardized z-scores. Associations between SPM families and incident MI were investigated in adjusted conditional logistic regressions stratified by T2DM status.
Results: While SPM concentrations were frequently below the detection limit, measurable levels of ≥1 SPM were identified in 298 participants. Seven SPMs were not detected in any participant and were excluded from subsequent analyses. Inverse trends were found for Resolvins-EEPA (ORnoT2DM=1.20(0.86,1.69); ORT2DM=0.55(0.24,1.26)) and Resolvins-Dn-3DPA (ORnoT2DM=0.96(0.71,1.29); ORT2DM=0.67(0.38,1.18)), which were stronger in individuals with T2DM. By contrast, positive trends with MI risk were found for ProtectinsDHA, Resolvins-Tn-3DPA and LipoxinsAA.
Discussion/Conclusion: Despite generally low SPM concentrations, higher levels of Resolvins-EEPA and Resolvins-Dn-3DPA were associated with lower MI risk, especially in individuals with T2DM, supporting the cardioprotective and inflammation-resolving roles of SPMs. Positive associations for other SPMs may reflect compensatory responses to increased CVD risk. While these findings should be interpreted cautiously, they justify further investigations into the role of SPMs on MI in individuals with and without T2DM.
Keywords: Specialized pro-resolving mediators; Incident myocardial infarction; Type 2 diabetes status; Case-control study; Inflammation resolution
Main source of funding:
Partly financed by NWO, within the EU ERA4Health CARDINNOV programme (GA N° 101095426), 2023 EFSD and Sanofi European Diabetes Research Programme in diabetes associated with cardiovascular disease, and COST Action EU-RESOLVE CA24138.
Potential disclosures: None