PROSPECT II Substudy: Relationship Between Different Levels of hs-CRP and Vulnerable Plaque Characteristics in Patients with NSTEMI

Inflammation plays a key role in the onset and progression of atherosclerosis and has been linked to a higher risk of cardiovascular events, regardless of cholesterol levels. High-sensitivity C-reactive protein (hs-CRP) is an acute-phase reactant that serves as a marker of systemic inflammation.

In a study involving 502 patients with documented coronary artery disease randomized to moderate- or high-intensity statin therapy, intravascular ultrasound (IVUS) was performed at baseline and after 18 months of follow-up. 

A reduction in hs-CRP levels over time was independently associated with regression in atheroma plaque volume. In another IVUS study in patients with acute coronary syndromes or stable chronic angina, baseline hs-CRP levels >3 mg/L were associated with a higher incidence of major adverse cardiac events (MACE) over 12 months of follow-up.

The aim of this substudy of PROSPECT II—a prospective, multicenter study—was to determine whether baseline levels of hs-CRP, as an inflammatory marker, were associated with the prevalence of high-risk, non-obstructive plaque and future cardiovascular events.

The primary endpoint (PEP) was the association between baseline hs-CRP levels and plaque morphology (lipid content, plaque burden, and lumen area) in 501 patients with non-ST segment elevation myocardial infarction (NSTEMI). hs-CRP levels were categorized as low (<1 mg/L), intermediate (1–3 mg/L), and high (>3 mg/L).

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The mean patient age was 63 years, and most subjects were men. The average baseline hs-CRP level was 3.1 mg/L. Most patients had high levels (50%), followed by intermediate (36%) and low (13%) levels. The percentage of patients with at least one high lipid plaque increased from 39.4% in the low hs-CRP group to 57.2% in the intermediate group and 59.3% in the high group (P = 0.01). The proportion of patients with a plaque burden ≥70% also increased progressively with hs-CRP levels: 22.7%, 27.2%, and 36.7%, respectively (P = 0.01).

Multivariable analyses showed that elevated hs-CRP levels were associated with a higher total lipid burden index in the coronary arteries and with greater plaque volume. A high hs-CRP level increased the likelihood of high lipid plaque and plaque volume equal to or above 70%.

Conclusion

These findings support the association between inflammation, high-risk plaque formation, and future cardiovascular risk. In patients with recent NSTEMI, elevated baseline hs-CRP was independently associated with high-risk atherosclerosis and the presence of focal vulnerable plaque. Systematic assessment of inflammatory risk, together with plaque characterization using intravascular imaging, provides valuable prognostic information beyond traditional risk factors.

Original Title: Relationships of hsCRP to High-Risk Vulnerable Plaque After NSTEMI Insights From the PROSPECTII Trial.

Reference: Ole Fröbert, MD et al JACC Cardiovasc Interv. 2025; 18:1217–1228.