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Published on: January 28, 2020
Peripheral blood endothelial microparticles (CD144+) as a surrogate marker for coronary microcirculatory dysfunction
Dao-Kuo Yao1, Xiao-Song Ding1, Bing Hua1
1Department of Cardiology, Beijing Friendship Hospital, Capital Medical, University, Beijing, China.
Insights
Circulating endothelial microparticles (EMPs) show a strong correlation with the index of microcirculatory resistance (IMR) in stable coronary artery disease (CAD). This suggests EMPs may serve as a promising non-invasive marker for coronary microvascular dysfunction (CMD).
Area of Science:
- Cardiovascular Medicine
- Biomarkers
- Diagnostic Tools
Background:
- Coronary microvascular dysfunction (CMD) is a significant cause of myocardial ischemia in stable coronary artery disease (CAD), often independent of epicardial stenoses.
- The index of microcirculatory resistance (IMR) is the gold standard for invasive CMD assessment but is limited by procedural complexity and cost.
- There is a need for non-invasive biomarkers to accurately assess CMD in clinical practice.
Purpose of the Study:
- To investigate the correlation between circulating endothelial microparticles (EMPs, CD144+) and invasive IMR in patients with stable CAD.
- To evaluate the potential of EMPs as a non-invasive surrogate marker for diagnosing CMD.
Main Methods:
- Fifty stable CAD patients and 20 controls underwent invasive assessment including IMR, fractional flow reserve (FFR), and coronary flow reserve (CFR).
- Peripheral venous blood samples were analyzed for CD144+ EMPs using flow cytometry.
- Statistical analyses, including correlation and ROC curve analyses, were performed to assess the association between EMPs and physiological indices.
Main Results:
- Circulating EMP counts were significantly higher in CAD patients compared to controls (145.62 vs. 119.98 particles/μL, P < 0.001).
- EMP levels showed a strong positive correlation with IMR in the CAD cohort (r=0.684, P < 0.001), but not in controls.
- EMPs demonstrated moderate diagnostic utility for CMD (IMR ≥ 23) with an AUC of 0.76, a sensitivity of 70.0%, and specificity of 70.6% at a threshold of 130 particles/μL.
Conclusions:
- Circulating CD144+ EMPs are strongly correlated with invasive IMR in stable CAD, suggesting their potential as a non-invasive biomarker.
- The moderate diagnostic performance and high negative predictive value of EMPs indicate promise for screening CMD.
- Further prospective validation in larger, multi-center studies is required before clinical implementation.
Objectives:
In stable coronary artery disease (CAD), coronary microvascular dysfunction (CMD) is a prevalent cause of myocardial ischemia independent of epicardial stenoses. Although the index of microcirculatory resistance (IMR) is the invasive reference standard for CMD assessment, its routine use is limited by procedural demands and cost. We investigated whether circulating endothelial microparticles (EMPs, CD144+) correlate with IMR and could serve as a non-invasive surrogate for CMD in stable CAD.
Methods:
Fifty patients with stable CAD and 20 controls with normal angiograms underwent invasive physiological assessment, including IMR, fractional flow reserve (FFR), and coronary flow reserve (CFR), using a pressure-temperature sensor-tipped guidewire. Peripheral venous blood was analyzed for CD144+ EMPs by flow cytometry. Associations between EMPs and physiological indices were evaluated, with diagnostic utility assessed via ROC curve analyses.
Results:
Demographic and clinical profiles were similar across groups (all P > 0.05). Circulating EMP counts were markedly higher in CAD patients than controls (145.62 ± 101.35 vs. 119.98 ± 71.93 particles/μL, P < 0.001), paralleled by elevated IMR values (22.14 ± 7.42 vs. 16.4 ± 4.41, P = 0.002). Within the CAD cohort, EMP levels correlated positively with IMR (r = 0.684, P < 0.001), but not in controls (r = 0.066, P = 0.783). Neither FFR nor CFR was associated with EMPs. Patients with IMR ≥ 23 had significantly higher EMP concentrations than those with IMR < 23 (P < 0.001). For discriminating CMD (IMR ≥ 23), EMPs yielded an AUC of 0.76 (95% CI: 0.62-0.89); at the optimal threshold of 130 particles/μL, sensitivity was 70.0%, specificity 70.6%, and negative predictive value 85.7%.
Conclusions:
Circulating CD144+ EMPs strongly correlate with invasive IMR in stable CAD. The moderate ROC performance (AUC 0.76) and high NPV suggest that peripheral EMP measurement holds promise as a non-invasive screening tool for CMD. However, these findings are exploratory and require prospective validation in larger, multi-center cohorts before clinical translation.
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