Association between remnant cholesterol and arterial stiffness: Evidence from NHANES 1999-2018

Nutr Metab Cardiovasc Dis. 2025 Aug;35(8):104013. doi: 10.1016/j.numecd.2025.104013. Epub 2025 Mar 27.

Abstract

Background and aim: Remnant cholesterol (RC), an emerging cardiovascular risk factor, has garnered increasing attention in atherosclerotic cardiovascular disease (ASCVD) research, though its relationship with arterial stiffness remains incompletely understood. This study investigated the association between RC and estimated pulse wave velocity (ePWV), a reliable marker of arterial stiffness, with the goal of enhancing our understanding of RC's role in cardiovascular risk assessment.

Methods and results: This study utilized the National Health and Nutrition Examination Survey (NHANES) data from 1999 to 2018, including 12,505 participants aged 20 years and above. Weighted linear regression, restricted cubic splines (RCS), and subgroup analyses were used to explore the association between RC levels and ePWV. Analysis revealed a significant positive association between RC levels and ePWV, with participants in the highest RC quintile (Q5) exhibiting substantially elevated ePWV compared to those in the lowest quintile (Q1). Notably, RCS analysis demonstrated a non-linear relationship characterized by a saturation effect (p-nonlinear <0.05). Subgroup analyses indicated stronger associations among specific demographic groups, including individuals under 40 years, females, non-Hispanic whites, and those above the poverty level (all interaction p < 0.05). Furthermore, mediation analysis found that various inflammatory markers such as neutrophil count (NEU), neutrophil-to-lymphocyte ratio (NLR), and monocyte-to-lymphocyte ratio (MLR) played a mediating role in this association.

Conclusion: Increased arterial stiffness is associated with higher RC levels, demonstrating a saturation effect at elevated concentrations. This association is partially mediated by NLR, MLR, and NEU, and was stronger among younger, females, non-Hispanic whites, and non-impoverished individuals.

Keywords: Arteriosclerosis vascular disease (ASCVD); Estimated pulse wave velocity (ePWV); National health and nutrition examination survey (NHANES); Remnant cholesterol (RC).

MeSH terms

  • Adult
  • Aged
  • Biomarkers / blood
  • Cardiovascular Diseases* / blood
  • Cardiovascular Diseases* / diagnosis
  • Cardiovascular Diseases* / epidemiology
  • Cardiovascular Diseases* / physiopathology
  • Cholesterol* / blood
  • Cross-Sectional Studies
  • Female
  • Heart Disease Risk Factors
  • Humans
  • Male
  • Middle Aged
  • Nutrition Surveys
  • Pulse Wave Analysis
  • Risk Assessment
  • United States / epidemiology
  • Vascular Stiffness*
  • Young Adult

Substances

  • Biomarkers
  • Cholesterol