Relation of C-Reactive Protein Levels to Instability of Untreated Vulnerable Coronary Plaques (From the PROSPECT Study)
What is the association between C-reactive protein (CRP) levels to instability of untreated vulnerable coronary plaques?
In the PROSPECT study, 697 patients with acute coronary syndromes (ACS) underwent percutaneous coronary intervention followed by three-vessel angiography, grayscale intravascular ultrasound (IVUS), and radiofrequency IVUS. Major adverse cardiac events (MACE) during 3 years of follow-up were adjudicated to initially treated culprit lesions or to untreated nonculprit lesions (NCLs). NCLs at greatest risk of causing subsequent MACE had plaque burden ≥70%, minimal luminal area (MLA) ≤4.0 mm2, and/or thin-cap fibroatheroma (TCFA) phenotype by radiofrequency IVUS. The authors examined the interaction of high-risk NCLs with CRP levels, which were measured at presentation, 1 month, and 6 months, then categorized at each time as normal (<3 mg/L), elevated (3-10 mg/L), or very elevated (>10 mg/dl).
The investigators found that patients with elevated CRP levels at any time did not have more high-risk NCLs; however, untreated high-risk NCLs were more likely to cause subsequent MACE in patients with very elevated compared to normal 6-month CRP levels (for TCFAs, 13.8% vs. 1.9%, p = 0.0003; for MLA ≤4.0 mm2, 15.6% vs. 2.2%, p < 0.0001). As expected, patients with very elevated 6-month CRP levels had higher rates of subsequent NCL-related MACE (19.0% vs. 7.2%, p = 0.039).
The authors concluded that the higher rates of NCL-related MACE among post-ACS patients with very elevated CRP levels may reflect greater instability of high-risk NCLs, rather than a larger burden of such lesions.
This PROSPECT trial substudy confirms the previously described association between CRP levels and subsequent MACE while adding two novel findings. Plaques with certain high-risk features, such as TCFA phenotype or MLA ≤4.0 mm2, were more likely to cause NCL-related MACE between 6 months and 3 years when they occurred in patients with very elevated 6-month CRP levels, and patients with very elevated 6-month CRP levels had a similar burden of these untreated high-risk NCLs as patients with normal levels. Ongoing research is examining whether drugs with anti-inflammatory effects, can affect the incidence of adverse cardiac events and, if so, the role of CRP in selecting patients for treatment or for monitoring response. Results of those studies will help further define the role of CRP in individuals at risk for cardiovascular events.
Keywords: Acute Coronary Syndrome, C-Reactive Protein, Follow-Up Studies, Plaque, Atherosclerotic, Phenotype, Research Personnel, Percutaneous Coronary Intervention
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