Infrapopliteal Calcium Score for PAD

Clinical Utility of Infrapopliteal Calcium Score for the Evaluation of Severity of Peripheral Artery Disease

Clinical question

To identify associations between computed tomography (CT)–based lower-extremity calcium score (LECS) across different anatomic segments and the presence, severity, and clinical outcomes of peripheral artery disease (PAD).

Take away point

An infrapopliteal calcium score of >188 Agatston units was associated with increased odds of having CLTI and was a potent predictor of CLTI and all-cause mortality among claudicants who were prospectively followed.

Reference

Lee, Sujin, Mari Tanaka, Shiv Patel, Nikolaos Zacharias, Sandeep Hedgire, Rajeev Malhotra, and Anahita Dua. "Clinical Utility of Infrapopliteal Calcium Score for the Evaluation of Severity of Peripheral Artery Disease." Journal of Vascular and Interventional Radiology 35, no. 3 (2024): 370-376.

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Study design

Retrospective multi-institutional database with a prospective component for model validation

Funding Source

None reported

Setting

Academic

Figure

Kaplan–Meier and Cox proportional hazards analysis of chronic limb-threatening ischemia (CLTI) and death among claudicants. Patients with an infrapopliteal calcium score of ≥188 had a significantly higher risk of progressing to CLTI or death compared with those with a calcium score of <188 (log-rank P = .0036). On the univariate Cox proportional hazards model, an infrapopliteal calcium score of ≥188 was associated with a hazard ratio of 5.58 for CLTI or death (P = .0095). LECS = lower-extremity calcium score.

Summary

Vascular calcification is a key feature of atherosclerotic cardiovascular disease, the leading global cause of morbidity and mortality. In peripheral artery disease (PAD), calcification in the lower extremities correlates with increased severity of ischemia and heightened risk of amputation. Despite evidence linking calcification in specific segments to adverse outcomes, the relationship between calcification at different anatomical sites and peripheral artery disease symptom severity remains unclear. This knowledge gap is particularly relevant as current guidelines recommend intervention only at advanced stages of peripheral artery disease symptoms. There is a need for quantitative markers. This study aims to establish associations between computed tomography-based lower-extremity calcium scores and peripheral artery disease symptom presence and severity, to enhance risk assessment and facilitate timely intervention.

This study utilized a multi-institutional database to evaluate patients who underwent CT angiography of the aorta and bilateral lower-extremity runoff between January 2016 and January 2020. Patients were categorized based on documented symptoms, including claudication, ischemic rest pain, and ulcers. A total of 139 patients met inclusion criteria. Lower-extremity calcium scores (LECSs) were quantified using the Agatston method on CT angiography images. Additionally, ankle-brachial index (ABI) and toe-brachial index (TBI) values obtained within 6 months of the CT scan were included. The optimal cutoff point for infrapopliteal calcium score in identifying patients with chronic limb-threatening ischemia (CLTI) was determined using the Youden J statistic and validated using bootstrapping technique. A prospective cohort of claudicants was followed until October 2022 for CLTI and all-cause mortality.

Multivariable analysis identified only hemodialysis and lower ankle-brachial index (ABI) as independent factors associated with increased odds of claudication. Lower-extremity calcium score in any of the anatomic segments was not independently associated with having claudication. On the other hand, multivariable analysis confirmed the independent association of high infrapopliteal calcium scores with CLTI, along with inability to perform daily activities and absence of hemodialysis dependence. Receiver operating characteristic analysis demonstrated improved predictive accuracy for CLTI when including infrapopliteal calcium scores in the model. Prospective follow-up of claudicants revealed that those with infrapopliteal calcium scores ≥188 Agatston units had a significantly higher risk of progressing to CLTI or death compared to those with lower scores. Cox proportional hazards analysis confirmed infrapopliteal calcium score as a robust predictor of CLTI-free survival, even after adjusting for potential confounders.

Arterial calcification is an independent risk factor for cardiovascular morbidity and mortality, but its impact on lower-extremity vasculature remains less understood. CT-based quantification of lower-extremity arterial calcification provides valuable information for risk stratification in PAD patients. Higher infrapopliteal calcium scores may identify patients at earlier stages of disease progression, enabling timely interventions to prevent CLTI and associated adverse outcomes.

Limitations of the study include its small sample size and retrospective design. Additionally, certain factors such as hemodialysis and surgical bypass procedures may confound the associations observed. Further prospective studies with larger cohorts are needed to validate the utility of infrapopliteal calcium score in evaluating peripheral arterial disease progression and guiding clinical management.

Commentary

This is a well done and well written study on the clinical utility of CT lower extremity calcium score for the evaluation of peripheral arterial disease. The methods and statistical analyses were appropriate and the prospective validation was appreciated. The findings have several implications for the management of peripheral arterial disease. First, infrapopliteal calcium score can serve as a prognostic indicator, enabling clinicians to identify claudicants who are at highest risk of disease progression. Second, infrapopliteal calcium scores can inform clinical decision-making regarding the timing and type of interventions. Overall, this study underscores the potential of CT-based lower-extremity arterial calcium score as a valuable tool in the evaluation and management of peripheral arterial disease. Further research and validation studies are warranted to confirm these findings and integrate infrapopliteal calcium scoring into clinical practice effectively.