Abstract Body: Introduction: Diet and genetics are key determinants of coronary artery disease (CAD). A pro-inflammatory diet, quantified by the Dietary Inflammatory Index (DII), and inherited susceptibility, quantified by a polygenic risk score (PRS), are independent risk factors for CAD. However, their interactive effect on long-term CAD risk is not well established.
Hypothesis: We assessed the hypothesis that a pro-inflammatory diet is associated with a higher risk of incident CAD, and that this association is potentiated by an individual's genetic susceptibility, as measured by a CAD-PRS.
Methods: We studied 2,856 participants from the Framingham Offspring Study free of prevalent cardiovascular disease at baseline (1991-1995). A validated food-frequency questionnaire was used to calculate DII scores. A genome-wide PRS for CAD was constructed. Participants were followed for incident CAD (myocardial infarction, coronary insufficiency, or CAD death). We used multivariable Cox proportional hazards models to assess the independent and joint associations of DII and PRS tertiles with CAD risk, adjusting for established risk factors. A multiplicative interaction term was tested.
Results: Over a median follow-up of 22 years, 467 incident CAD events occurred. In fully adjusted models, both the highest DII tertile (HR: 1.45; 95% CI: 1.15-1.83) and the highest PRS tertile (HR: 1.70; 95% CI: 1.35-2.14) were independently associated with increased CAD risk compared to their respective lowest tertiles. A significant statistical interaction was observed between DII and PRS (p−interaction=0.015). The effect of DII was most pronounced among those with high genetic risk. Compared to individuals with low DII and low PRS, those with high DII and high PRS had a nearly threefold increased risk of incident CAD (HR: 2.84; 95% CI: 1.82-4.43).
Conclusions: In conclusion, a pro-inflammatory diet is associated with an increased risk of incident CAD, particularly among individuals with a high genetic predisposition. These findings suggest that adopting an anti-inflammatory diet may be a particularly effective strategy for mitigating CAD risk in genetically susceptible individuals, supporting a role for precision nutrition in cardiovascular prevention.