Association between neutrophil count, LDL-C, and long-term carotid plaque progression

Background Carotid plaque progression is strongly associated with cardiovascular events. Accumulating evidence indicates increased inflammation and lipids are key contributors to atherosclerosis progression. Although previous studies have shown the prognostic value of neutrophil count and LDL-C in cardiovascular risk prediction, their longitudinal associations with subclinical carotid plaque dynamics remain incompletely characterized. Purposes This study aims to determine the independent associations of baseline neutrophil count and LDL-C with carotid plaque progression over long-term follow-up in a community-based cohort. Additionally, the synergistic effects of these biomarkers on plaque progression were investigated. Methods Participants from the ARIC study with complete baseline (1987) and follow-up (1998) data on neutrophil counts, LDL-C levels, and carotid ultrasound were enrolled. Neutrophil counts and LDL-C were categorized into quartiles. The carotid plaque score (CPS, range: 0–6) was derived from six arterial segments (common carotid, bulb, and internal carotid arteries bilaterally), with one point per segment if plaque was present. Participants with ΔCPS > 0 were classified as plaque progressors. Cox proportional hazard models assessed associations between neutrophil counts, LDL-C, and plaque progression, while multivariable logistic regression evaluated risk factor contributions. Joint analyses determined if combined biomarkers improved plaque progression prediction. Results Among 11,139 participants, 1,231 (11.0%) demonstrated carotid plaque progression. The mean age at baseline was 53.21 ± 5.66 years. Progressors were more likely to be older, smokers, have higher systolic blood pressure, and a higher prevalence of comorbidities (P < .05 for all). After adjusting for covariates, a significant association was observed between neutrophil count and plaque progression, particularly in participants in the fourth quartile (HR 1.23, 1.03-1.47, P = .019) (Figure 1A). LDL-C levels showed a progressive association with plaque progression across quartiles, with HR and 95% CI of 1.26 (1.06-1.49), 1.32 (1.12-1.57), and 1.36 (1.15-1.61) for Q2, Q3, and Q4, respectively (P < .01 for all) (Figure 1A). Logistic regression analysis revealed that LDL-C (χ² = 18.13, P < .0001) and neutrophil count (χ² = 7.28, P = .006) significantly contributed to the risk of plaque progression (Figure 1B). In joint analyses (Figure 2), plaque progression risk increased progressively with higher neutrophil counts across LDL-C quartiles and with higher LDL-C levels across neutrophil quartiles, peaking with concomitant elevation of both neutrophil count (Q4) and LDL-C (Q4) (HR 2.65, 1.86-3.77, P < .01). Conclusions Neutrophil count and LDL-C demonstrate both independent and synergistic associations with long-term carotid plaque progression. Integrating inflammatory and lipid profiles may enhance risk stratification for subclinical atherosclerosis.