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Assessment of N/L ratio and subclinical atherosclerosis in FH subjects with or without LDLR mutation

Francesco Di Giacomo Barbagallo1,2, Giosiana Bosco1,2, Maurizio Di Marco1

  • 1Department of Clinical and Experimental Medicine, University of Catania, Catania 95123, Italy.

Journal of the Endocrine Society
|February 17, 2026
PubMed

Insights

Familial hypercholesterolemia (FH) patients with LDLR mutations show higher neutrophil-to-lymphocyte ratio (NLR) and more severe atherosclerosis. This suggests NLR is a biomarker for early immune activation in FH.

Area of Science:

  • Cardiovascular Medicine
  • Genetics
  • Immunology

Background:

  • Familial hypercholesterolemia (FH) is a genetic disorder causing high LDL-C and cardiovascular risk.
  • The role of inflammation in FH, especially concerning genotype, is not well understood.
  • This study investigates genotype's impact on inflammation markers and atherosclerosis in FH patients.

Purpose of the Study:

  • To evaluate the impact of genotype on neutrophil-to-lymphocyte ratio (NLR) in FH subjects.
  • To assess the association between genotype and subclinical atherosclerosis in FH.
  • To explore NLR as a potential biomarker for immune activation in FH.

Main Methods:

  • Cross-sectional study of 423 FH patients without lipid-lowering therapy or existing cardiovascular disease.
  • Genotyping categorized patients into low-density lipoprotein receptor (LDLR) and non-LDLR groups.
  • Vascular assessments included coronary artery calcium score and plaque presence; NLR was calculated from blood counts.

Main Results:

  • The LDLR group had a significantly higher NLR compared to the non-LDLR group (2.27 vs 2.05, P < .05).
  • Both LDL-C levels and LDLR genotype were significantly associated with NLR (P < .05).
  • Multiterritorial plaque involvement was more frequent in the LDLR group, and NLR independently predicted subclinical atherosclerosis.

Conclusions:

  • FH patients with LDLR mutations exhibit elevated NLR and more severe atherosclerosis.
  • NLR serves as a noninvasive biomarker for early immune activation in FH.
  • Evaluating lipoinflammatory status is crucial for managing FH patients.
Abstract

Keywords:
LDL receptorcardiovascular riskfamilial hypercholesterolemiainflammationneutrophil-to-lymphocyte ratiosubclinical atherosclerosis

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