Coronary microvascular dysfunction is associated with higher frequency of thin-cap fibroatheroma.

Objective: Both coronary microvascular dysfunction and epicardial plaque vulnerability have been associated with adverse cardiovascular outcomes. However, whether microvascular dysfunction is a predictor of plaque vulnerability is not known. We hypothesized that microvascular dysfunction is associated with greater systemic inflammation and is a predictor of virtual histology-intravascular ultrasound (VH-IVUS)-defined coronary thin-cap fibroatheromas.

Methods: Invasive physiologic assessment and VH-IVUS were performed and serum high-sensitivity C-reactive protein (hs-CRP) was measured in 51 patients with non-obstructive CAD [fractional flow reserve (FFR)≥0.75]. Microvascular dysfunction was defined as coronary flow velocity reserve (CFVR)<2.0. Lumen area and plaque burden and composition were assessed in each VH-IVUS frame. Frequency of thin-cap fibroatheroma (TCFA) in each artery was defined as the percentage of VH-IVUS frames with plaque burden≥40% and confluent necrotic core≥10% in contact with lumen for at least 3 consecutive frames.

Results: Mean age was 57±12 years and 25% of patients presented with acute coronary syndrome. Despite similar amount of epicardial disease, characterized by lumen area (8.9±3.0 vs. 10.1±3.3mm(2), p=0.3) and FFR (0.90±0.08 vs. 0.92±0.07, p=0.2), patients with microvascular dysfunction had greater hs-CRP (4.2 [2.3, 7.6] vs. 1.0 [0.4, 4.2]ng/ml, p=0.006), greater plaque burden (47±10 vs. 36±13%, p=0.004), and higher frequency of TCFA (17±25 vs. 6±9%, p=0.02). After adjustment for cardiovascular risk factors, hs-CRP, and plaque burden, coronary microvascular dysfunction was an independent predictor of frequency of TCFA (β=+0.42, p=0.033).

Conclusion: In patients with non-obstructive CAD, coronary microvascular dysfunction is associated with higher serum hs-CRP and is an independent predictor of more TCFAs, a marker for increased epicardial plaque vulnerability.