Healthy diet attenuates the cardiovascular risk associated with elevated monocytes: a prospective cohort study

Elevated monocyte counts predict cardiovascular disease (CVD) risk, but whether this inflammatory risk is modifiable by dietary patterns remains unknown. We investigated whether dietary quality modifies the association between peripheral monocyte counts and incident CVD and explored potential proteomic mechanisms.

This prospective cohort study included 26,585 participants from the UK Biobank without baseline CVD. Dietary quality was assessed using a Diet Quality Index (DQI) incorporating processed meat, fish, and plant-based food consumption. Monocyte counts were measured at baseline. Cox proportional hazards models with restricted cubic splines were used to examine the dose-response relationship between monocyte counts and CVD risk, stratified by dietary quality. Joint analyses evaluated combined effects of high monocyte counts and unhealthy diet on CVD outcomes. Proteome-wide interaction analysis was performed to identify plasma proteins linking diet-immune interactions to CVD risk.

During a median follow-up of 16.2 years, 1,834 CVD events occurred. Elevated monocyte counts were associated with increased CVD risk (HR per SD: 1.28, 95% CI: 1.11-1.48, p = 0.0009). A significant interaction was observed between monocyte count and dietary quality (P interaction = 0.04). Joint analysis revealed that participants with high monocyte counts and unhealthy diet faced the highest risk (HR: 1.18, 95% CI: 1.03-1.35), while those with high monocyte counts but healthy diet showed no excess risk (HR: 1.04, 95% CI: 0.91-1.20). In an exploratory proteome-wide interaction screen, Regenerating islet-derived protein 4 (REG4) was identified as the top nominal interaction signal (P interaction = 2.69 × 10^-5; FDR q = 0.079), though this did not survive multiple testing correction. High diet quality substantially attenuated the positive association between monocytes and pro-inflammatory REG4 levels observed in unhealthy eaters.

Dietary quality modulates the association between peripheral monocyte counts and cardiovascular disease risk, potentially involving downstream inflammatory proteins such as REG4, though this proteomic finding remains exploratory. For individuals with elevated inflammatory burden, adherence to a healthy diet represents a practical strategy to mitigate excess cardiovascular risk.