Association of C-Reactive Protein With Dense Calcium and Fibro-Fatty Plaque on Intravascular Ultrasound Virtual Histology in Critical Limb-Threatening Ischemia Patients

Abstract

Objectives:

To identify potential pathophysiological connections between intravascular ultrasound virtual histology (IVUS-VH) analyzed plaque characteristics and laboratory data while verifying possible connections with long-term clinical outcomes in real-world clinical practice.

Materials and Methods:

This retrospective study analyzed clinical data from 54 consecutive patients undergoing endovascular therapy (EVT) in our department between June 2019 and June 2023. The data set encompassed comprehensive parameters including IVUS-VH imaging findings, laboratory data, procedural details of interventional treatments, and post-operative clinical outcomes. Patients’ IVUS-VH data were analyzed in relation to laboratory data (D-dimer, C-reactive protein [CRP], triglycerides, total cholesterol, NRL, etc) and clinical outcomes (ABI change, survival rate, major amputation rate, primary patency, and re-intervention rate).

Results:

The average age of the 54 patients is 66.8±11.2 years old. Among them, 35 patients (64.8%) experienced rest pain, and 19 patients (35.2%) experienced claudication. All patients successfully underwent IVUS and IVUS-VH. General IVUS data for the most severe sections included: minimal area 4.4±2.2 mm², minimal diameter 2.0±0.5 mm, total lesion area 24.6±7.2 mm², and plaque burden 86.6±5.7%. The IVUS-VH data includes (1) the fibrotic plaque area, which is 13.3±5.3 mm²; (2) the Fibro-fatty area, which is 9.1±4.0 mm²; (3) the necrotic core area, which is 1.8±1.5 mm²; and (4) the dense calcium area, which is 0.5±0.5 mm². During the correlation analysis of IVUS-VH data, we find that a significant negative correlation between dense calcium and fibro-fatty plaque area (r=−0.380, p=0.005; q=0.028). In addition, the CRP levels were significantly positively correlated with dense calcium area (r=0.411, p=0.004; q=0.024) and negatively correlated with fibro-fatty plaque area (r=−0.324, p=0.026; q=0.048).

Conclusions:

In CLTI patients, dense calcium and fibro-fatty plaque areas are negatively correlated in IVUS-VH data. The CRP levels are positively correlated with dense calcium lesion area and negatively correlated with fibro-fatty plaque lesion area in CLTI patients. These findings are consistent with research in coronary arteries. This study did not find correlations between IVUS-VH data and other clinical outcomes; however, a larger data set and longer follow-up may provide new insights in the future.

Clinical Impact

This study provides insights into plaque phenotyping in chronic limb-threatening ischemia (CLTI) by demonstrating correlations between C-reactive protein (CRP) levels and specific intravascular ultrasound-virtual histology (IVUS-VH) plaque components (dense calcium and fibro-fatty tissue). This suggests that CRP, a readily available biomarker, may reflect underlying plaque morphology in peripheral arteries, similar to coronary findings. Clinically, these results highlight the potential of integrating systemic inflammatory markers with advanced imaging for more comprehensive risk assessment. Although not yet predictive of long-term outcomes, this integrative approach represents a step toward personalized therapy in CLTI and encourages future research into interventions targeting specific plaque compositions.