BACKGROUND AND AIMS: Several studies have supported the role of innate immune system as a key factor in the sterile inflammation underlying the pathophysiology of atherosclerosis in mice. However, its involvement in humans remains unclear. This study aimed to explore the association between neutrophil count, and the intima-media thickness of common carotid arteries (IMT-CC), as well as the potential impact of long-term dietary interventions on these associations. METHODS: A comprehensive analysis was conducted within the framework of the CORDIOPREV study, a long-term secondary prevention study involving dietary interventions with either a Mediterranean or a low-fat diet. The study evaluated the relationship between absolute neutrophil count and neutrophil-related ratios with IMT-CC at baseline and after 5 and 7 years of dietary intervention. RESULTS: At baseline, patients in the highest tertile of neutrophil count had a higher IMT-CC and number of carotid plaques, when compared to lowest tertile (P <
.01 and P <
.05, respectively). Logistic regression analyses supported this association. Elevated neutrophil count, neutrophil-to-erythrocyte ratio, and neutrophil-to-HDL ratio were associated with an increased likelihood of having an IMT-CC >
.9 mm {odds ratio (OR) 1.17 [95% confidence interval (CI) 1.04-1.35], OR 2.21 (95% CI 1.24-4.12), and OR 1.96 (95% CI 1.09-3.55), respectively}, after adjustment for all variables, which was corroborated by linear regression. Furthermore, a linear mixed-effect model analysis from a longitudinal analysis spanning 5 and 7 years revealed an increase in 1 unit of neutrophils/μl at these time points was associated with a mean increase of .004 (.002) mm in the IMT-CC (P = .031) after adjustment for all variables. Interestingly, in patients exhibiting regression in IMT-CC after 7 years of follow-up, those following a Mediterranean diet showed a significant decrease in neutrophil count after 5 and 7 years (both with P <
.05), compared to baseline. CONCLUSIONS: These findings suggest that neutrophils may represent a promising target for preventing atherosclerosis. A Mediterranean diet could serve as an effective dietary strategy to reduce neutrophil levels and potentially slow the progression of atherosclerosis, offering a new neutrophil-reducing therapy concept. Further research is essential to gain deeper insights into the role of neutrophils in the pathophysiology of atherosclerotic cardiovascular disease in humans.