Work

Imbalances in circulating monocyte and high-density lipoprotein cholesterol exacerbates the residual risk of incident myocardial infarction beyond LDL-C: a real-life, prospective cohort study

Year: 2025

Type: article

Abstract: BACKGROUND: A sustained oversupply of monocytes and markedly decreased levels of high-density lipoprotein cholesterol (HDL-C) are notable in high-risk groups with residual cardiovascular risk, despite aggressive low-density lipoprotein cholesterol (LDL-C) lowering. This study aimed to explore whether an imbalance in circulating monocyte and HDL-C levels accounts for the residual risk of incident myocardial infarction (MI) within optimal LDL-C levels. METHODS: A total of 48,522 participants free of cardiovascular diseases from a real-life, prospective cohort (Kailuan study) were included. The monocyte count, HDL-C level and monocyte-to-HDL-C ratio (MHR), calculated as time-averaged cumulative and baseline values, were used as the exposures. Time-to-event survival analyses were conducted to examine the association between exposure and MI incidence, especially tests for risk heterogeneity across different LDL-C levels and other potential confounders. RESULTS: During a median follow-up of 10.06 years, 573 MI events occurred. An elevated time-averaged MHR was positively correlated with clustering of traditional risk factors but inversely correlated with LDL-C levels. After adjusting for potential confounders, each 1-SD increase in the time-averaged monocyte count, HDL-C level and MHR was significantly associated with a risk of 1.18 (95% CI: 1.08-1.28), 0.86 (95% CI: 0.79-0.93) and 1.27 (95% CI: 1.16-1.38), respectively. Individuals with LDL-C levels between 1.8 and 2.6 mmol/L had the lowest MI incidence but the highest MI risk (1.50, 95% CI: 1.27-1.79) with exposure to time-averaged MHR. In contrast, individuals with LDL-C levels ≥ 3.4 mmol/L had the highest MI incidence, but nonsignificant MI risk (HR: 0.99, 95% CI 0.82-1.19) was associated with time-averaged MHR. CONCLUSION: Chronic imbalances in monocyte and HDL-C levels are significantly associated with incident MI among individuals with low LDL-C levels. Longitudinally tracing MHR changes and targeting elevated MHR may help to optimize risk assessment and management of MI.

Source: Journal of Translational Medicine

DOI: 10.1186/s12967-025-07028-7