Mediterranean diet, neutrophil count, and carotid intima-media thickness in secondary prevention: the CORDIOPREV study

Abstract

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.

Structured Graphical Abstract

Structured Graphical Abstract

Increased neutrophils were associated with greater intima-media thickness of common carotid arteries (IMT-CC) both at baseline. Furthermore, the longitudinal analysis spanning 5 and 7 years revealed an increase in 1 unit of neutrophil value/μL at these time points is associated with a mean increase of .004 mm in the IMT-CC. Nonetheless, adherence to the Mediterranean Diet resulted in a reduction in neutrophil among patients who exhibited a decrease in IMT-CC after 7-year of follow-up, suggesting a novel neutrophil-reducing therapy strategy. IMT-CC, Intima-media thickness of common carotid arteries.

• Key Question: What is the clinical implication of neutrophils in atherosclerosis development over 5- and 7-year follow-up? Can dietary approaches, such as a Mediterranean diet, help reduce neutrophils and minimize this risk, suggesting a new therapeutic strategy?

• Key Findings: Increased neutrophils were associated with greater intima-media thickness of common carotid arteries (IMT-CC) both at baseline and after the longitudinal analysis. Nonetheless, adherence to the Mediterranean diet resulted in a reduction in neutrophils among patients who exhibited a decrease in IMT-CC after 7-year follow-up.

• Take Home Message: Neutrophils may serve as a therapeutic target for atherosclerosis prevention in humans. The Mediterranean diet, as a therapeutic strategy, could reduce neutrophils and slow atherosclerosis progression, supporting a novel neutrophil-reducing therapy plan.