Serologic Markers of Vulnerable Plaques and Patients
| Metabolic and immune disorders | Hypercoagulability | Complex atherosclerotic plaque |
|---|---|---|
| Abnormal lipoprotein profile [e.g., high LDL, low HDL, and Lp(a)] | Markers of blood hypercoagulability (e.g., fibrinogen, d-dimer, and factor V of Leiden) | Morphology and structure |
| Nonspecific markers of inflammation (e.g., hs-CRP, CD40L, ICAM-1, and VCAM-1), leukocytosis, and other immunologic and serologic markers that may not be specific for atherosclerosis and plaque inflammation | Increased platelet activation and aggregation (e.g., gene polymorphisms of platelet glycoproteins IIb/IIIa, Ia/IIa, and Ib/IX) | Cap thickness |
| Serum markers of metabolic syndrome (diabetes or hypertriglyceridemia) | Increased coagulation factors (e.g., clotting factors V, VII, VIII, and XIII and von Willebrand factor) | Lipid core size |
| Specific markers of immune system activation (e.g., anti-LDL antibody and anti–heat shock protein antibody) | Decreased anticoagulation factors (e.g., proteins S and C, thrombomodulin, and antithrombin III) | Percentage of stenosis |
| Markers of lipid peroxidation (e.g., OxLDL and oxidized HDL) | Decreased endogenous fibrinolytic activity (e.g., decreased tissue plasminogen activator, increased type I plasminogen activator [PAI], and PAI polymorphisms) | Remodeling (positive vs. negative) |
| Homocysteine | Prothrombin mutation (e.g., G20210A) | Color (yellow or red) |
| PAPP-A | Thrombogenic factors (e.g., anticardiolipin antibodies, thrombocytosis, sickle cell disease, diabetes, and hypercholesterolemia) | Collagen content vs. lipid content |
| Circulating apoptosis markers (e.g., Fas and Fas ligand) | Transient hypercoagulability (e.g., smoking, dehydration, and infection) | Calcification burden and pattern |
| ADMA and dimethylarginine dimethylaminohydrolase | Shear stress | |
| Circulating nonesterified fatty acids | Activity and function | |
| Plaque inflammation (macrophage density and rate of monocyte and activated T-cell infiltration) | ||
| Endothelial denudation or dysfunction (local NO production and anti- or procoagulation properties of endothelium) | ||
| Plaque oxidative stress | ||
| Superficial platelet aggregation and fibrin deposition | ||
| Rate of apoptosis (apoptosis protein markers and microsatellites) | ||
| Angiogenesis, leaking vasa vasorum, and intraplaque hemorrhage | ||
| MMPs (MMP-2, MMP-3, and MMP-9) | ||
| Microbial antigens (Chlamydia pneumoniae) | ||
| Temperature | ||
| Global features | ||
| Transcoronary gradient of vulnerability biomarkers | ||
| Total calcium burden | ||
| Total coronary vasoreactivity | ||
| Total arterial plaque burden (intima–media thickness) |