Physicians' Academy for Cardiovascular Education

High residual inflammatory risk associated with adverse clinical outcomes in patients undergoing PCI with low LDL-c

Residual Inflammatory Risk in Patients With Low LDL Cholesterol Levels Undergoing Percutaneous Coronary Intervention

Literature - Guedeney P, Claessen BE, Kalkman DN et al. - JACC 2019;73(19):2401-9

Introduction and methods

Patients with coronary artery disease undergoing percutaneous coronary intervention (PCI) show high ischemic risk. One of the strategies to lower adverse events is statin therapy to achieve low-density lipoprotein cholesterol (LDL-c) levels <70 mg/dL [1-3]. However, these patients may also have elevated residual inflammatory risk (RIR) pre- and post-PCI, which is associated with poor prognosis [4,5]. Data on lowering RIR obtained in the CANTOS trial have opened new perspectives in the field of secondary prevention [6,7]. The definition of RIR may be C-reactive protein (CRP) >2 mg/dL, while residual cholesterol risk is mostly defined as LDL-c ≥70 mg/dL [1,2,8].

This retrospective analysis characterized the prevalence of persistent high RIR in patients undergoing PCI in a high-volume tertiary care facility with controlled cholesterol risk and evaluated its link with clinical outcomes, using data from the prospective PCI-registry of a large-volume center (The Mount Sinai Hospital, New York, New York). Inclusion was based on PCI between Jan 1, 2009 and Dec 31, 2016, baseline LDL-c ≤70 mg/dL and ≥2 serial high-sensitive CRP (hsCRP) measurements ≥4 weeks apart. High inflammatory status was defined as hsCRP >2 mg/dL. Eligible patients (n= 3,013) were divided into groups based on RIR: persistent high RIR (high inflammatory status at baseline and follow-up), attenuated RIR (first high then low hsCRP), increased RIR (first low then high hsCRP), and persistent low (hsCRP ≤2 mg/dL at baseline and follow-up). The primary endpoint was the composite of major adverse cardiac and cerebrovascular events (MACCE) (all-cause death, MI, or stroke within 1 year following the second hsCRP measurement).

Main results

1-Year outcomes according to the residual inflammatory risk

High residual inflammatory risk associated with adverse clinical outcomes in patients undergoing PCI with low LDL-c


This single-center prospective PCI-registry showed high RIR in one-third of patients undergoing PCI with low LDL-c (≤70 mg/dL) at baseline, which was independently linked to adverse clinical outcomes, indicating the need of more research on inflammation modulating intervention in these patients.

Editorial comment

In his editorial comment, Everett [9] discusses the results obtained by Guedeney et al. that confirm and extend two important findings from previous studies: 1) RIR was observed in one-third of all post-MI patients, even if they have statin therapy or other aggressive LDL-c lowering treatments, and 2) there was an association of RIR and increased risk of MI, stroke and all-cause mortality. These observations suggest an important problem in patients with established coronary artery disease.

Everett explains that risk of MI, stroke or CV death can be reduced with IL-1β inhibition in patients with high RIR, as shown by the CANTOS trial. However, ‘canakinumab is not currently available for this indication in the United States’. In CANTOS, the effect of IL-1β inhibition on clinical outcomes was particularly seen in participants with reduced inflammation, with the greatest benefit found in those who achieved hsCRP <2 mg/dL. Researchers are developing new treatments directed at the NLRP3 inflammasome and its downstream signaling cascade, including IL-1β and IL-6. Everett concludes: ‘Future investigation should focus on identifying safe, efficacious, and affordable treatments for this important pathway of ongoing cardiovascular risk’.


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