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Background <p>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.</p> Methods <p>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.</p> Results <p>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.</p> Conclusion <p>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.</p>

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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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月30日

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  • Dan Wu,
  • Yulong Lan,
  • Xiong Ding,
  • Lois Balmer,
  • Xingang Li,
  • Wei Wang,
  • Shouling Wu,
  • Youren Chen

摘要

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.