The mediating effect of DHA-mediated MPV improvement on coronary artery stenosis and its prognostic value

Cardiovascular disease (CVD) remains a leading global health threat. The high incidence of coronary artery disease (CAD) is closely associated with atherosclerotic progression, and thrombosis mediated by platelet activation is a key mechanism triggering acute coronary events and contributing to the high mortality of CAD. Omega-3 polyunsaturated fatty acids (ω-3 PUFA) exert cardiovascular protective effects through anti-inflammatory and antiplatelet aggregation effects. However, their mechanisms underlying the regulation of coronary stenosis severity in CAD via platelet morphological parameters (mean platelet volume, MPV) and their prognostic value remain unclear. This study aims to investigate the association between serum DHA, EPA, and MPV with the onset of CAD, the severity of coronary artery stenosis (Gensini score), and the prognosis of major adverse cardiovascular events (MACE), while validating the mediating effect of MPV.

A total of 183 patients with coronary artery disease (CAD) and 189 controls were included. Baseline data were collected, and levels of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and arachidonic acid (AA) were measured by ultra-performance liquid chromatography-mass spectrometry. Logistic regression, Spearman correlation analysis, bootstrap mediation analysis, Kaplan-Meier survival analysis, and Cox proportional hazards regression were employed to explore the mechanisms and associations between omega-3 PUFAs, MPV, and CAD onset, coronary artery stenosis severity, and MACE.

Serum DHA levels were significantly lower in the CAD group than in controls (P < 0.001). Among CAD patients, DHA was significantly negatively correlated with MPV, platelet distribution width (PDW), and platelet large cell ratio (PLCR) (r = -0.169, -0.156, -0.186, all P < 0.05), while MPV, PDW, and PLCR were weakly positively correlated with Gensini scores (r = 0.170, 0.158, 0.165, all P < 0.05). Bootstrap mediation analysis confirmed that MPV showed a statistically significant mediating effect in the association between DHA and Gensini score, consistent with a mediation model (P = 0.034). Prognostic analyses demonstrated that DHA was an independent protective factor for MACE (HR = 0.83, 95% CI: 0.74-0.93, P = 0.002),MPV was an independent risk factor for MACE (HR = 1.22, 95% CI: 1.00-1.49, P = 0.046), and the combination of "high DHA (≥1.4127 μmol/L) + low MPV (≤10.4 fL)" significantly reduced the risk of MACE (Log-rank test, P = 0.0011).

DHA is associated with coronary stenosis severity, and this association is statistically consistent with partial mediation by MPV. The combined assessment of DHA and MPV optimizes risk stratification in CAD patients, providing quantitative evidence for personalized nutritional interventions with significant clinical translational value.