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Implications of inflammation and sex in lower extremity arterial disease
Katja Schnidrig1, Manovriti Thakur1,2, Aleksandra Tuleja1,3
1Division of Angiology, Swiss Cardiovascular Center, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
Insights
Inflammatory markers can predict lower extremity arterial disease (LEAD) progression and outcomes. Comprehensive profiling, including sex-specific analyses and machine learning, is crucial for tailored prevention and treatment strategies in LEAD patients.
Area of Science:
- Vascular Medicine
- Inflammation Biology
- Biomarker Discovery
Background:
- Lower extremity arterial disease (LEAD) impacts over 200 million globally, primarily due to chronic vascular inflammation.
- The intricate relationship between inflammatory pathways, prognostic significance, and sex-specific variations in LEAD is not fully understood.
Purpose of the Study:
- To explore the prognostic value of inflammatory markers in LEAD.
- To investigate potential sex-specific differences in inflammatory pathways and their impact on LEAD outcomes.
- To identify key inflammatory markers for risk stratification in LEAD.
Main Methods:
- Review of existing literature on inflammatory markers and LEAD.
- Analysis of established inflammatory markers (e.g., hs-CRP, fibrinogen, IL-6) and emerging parameters (e.g., neutrophil counts, clonal hematopoiesis markers).
- Consideration of sex-specific differences in disease presentation, lesion patterns, and marker associations.
Main Results:
- Elevated inflammatory markers (hs-CRP, fibrinogen, D-dimer, IL-6, α-defensins, soluble adhesion molecules, neutrophil counts, clonal hematopoiesis markers) are linked to LEAD onset and progression.
- LEAD patients, particularly women, may present with more advanced disease, distinct lesion patterns, and greater functional impairment.
- While women may have higher baseline CRP, the association between inflammatory markers and adverse outcomes can be attenuated compared to men.
Conclusions:
- Comprehensive inflammatory profiling is essential for LEAD risk stratification.
- Integrating sex-specific analyses, novel biomarkers, and machine learning is vital for future studies.
- Future research should combine clinical, genomic, proteomic, and functional data for personalized LEAD prevention and treatment.
Background:
Lower extremity arterial disease (LEAD) affects over 200 million people globally and is largely driven by chronic vascular inflammation. However, the complex interplay between inflammatory pathways, their prognostic value and potential sex-specific differences remains insufficiently understood.
Methods And Results:
Literature indicates that elevated inflammatory markers-such as (high-sensitivity) C-reactive protein, fibrinogen, D-dimer, interleukin-6, α-defensins and soluble adhesion molecules as well as newly arising parameters such as neutrophil counts and markers of clonal haematopoiesis-may predict both the onset and progression of LEAD, from declining ankle-brachial indices and impaired walking performance to higher rates of amputation, cardiovascular events and mortality. Moreover, women with LEAD frequently present at older ages with more advanced disease, exhibit distinct lesion patterns and greater functional impairment, and often have higher baseline CRP levels than men, although the strength of association between inflammatory markers and adverse outcomes may be attenuated in women. However, it remains unclear how inflammatory markers can guide (sex) specific patient stratification in LEAD or which markers provide the most clinical utility in general.
Conclusion:
Together, these findings underscore the need for comprehensive inflammatory profiling in LEAD risk stratification and highlight the importance of joining sex-specific analyses, new (bio)markers and machine learning to integrate clinical, genomic, proteomic and functional data into future studies to inform patient-tailored prevention and treatment strategies.
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