Abstract Background Atherosclerotic cardiovascular disease remains the leading cause of morbidity and mortality worldwide, with subclinical carotid plaque serving as a critical determinant of long-term cardiovascular risk. Inflammation plays a central role in the process of atherogenesis. Although the associations between elevated leukocyte counts and cardiovascular risk have been documented, the dynamic nature of inflammatory responses necessitates trajectory-based analysis. Furthermore, the differential impact of leukocyte trajectory patterns on major adverse cardiovascular events (MACE) among individuals with and without carotid plaque remains unclear. Purposes To identify distinct leukocyte trajectory patterns and evaluate their differential associations with MACE risk in individuals stratified by carotid plaque status. Methods Data were obtained from the ARIC study, including participants with complete leukocyte count measurements across three visits (1987–1995) and baseline carotid ultrasound assessment. The primary outcome was defined as MACE, including myocardial infarction, stroke, and cardiovascular death. Follow-up extended from Visit 2 through 2019, censored at first MACE occurrence. Group-based trajectory modeling identified distinct leukocyte trajectory patterns. Multivariable Cox proportional hazard models and survival analyses were applied to assess MACE risk. Results Among 2,342 participants (mean age 54.68 years; 53.97% male), 838 (35.8%) had carotid plaque at baseline. Individuals with plaques were more likely to be smokers, have higher cholesterol, higher glucose, and cardiovascular disease history (P .05). Four leukocyte trajectories were identified (Figure 1 A and B): low-stable, moderate-increasing, moderate-decreasing, and high-stable. Over a median follow-up of 25.8 years, MACE occurred in 33.3% of participants with carotid plaque and 16.42% without plaque. After adjusting for confounders, the high-stable group showed a significant association with MACE incidence in individuals with carotid plaque (HR 1.43, 1.05-1.73, P = .03), compared to the low-stable pattern (P .05) (Figure 1C and Figure 2A). Among individuals without carotid plaque, elevated risk with moderate-decreasing (HR 1.67, 1.13-2.83, P .05) and high-stable (HR 2.02, 1.30-3.14, P .05) trajectories were observed (Figure 1D). Survival curves revealed temporal divergence: moderate-decreasing trajectories exhibited early risk elevation, while moderate-increasing trajectories manifested late risk (Figure 2B). Conclusion The high-stable leukocyte trajectory pattern reflects sustained inflammatory exposure and serves as an independent risk factor for MACE irrespective of carotid plaque status. Fluctuations of leukocytes predict cardiovascular risk in individuals without carotid plaque. These findings underscore the prognostic value of longitudinal inflammatory monitoring for refined risk stratification.
Yang et al. (2025) studied this question.