A recent study published in the European Heart Journal showed that a high percentage of patients undergoing percutaneous coronary intervention (PCI) had persistently high residual inflammatory risk (RIR). Moreover, high RIR was associated with increased all-cause mortality and myocardial infarction (MI) risk at 1 year of follow-up.
When asked about the consensus of evidence regarding the prognostic value of RIR, Dr. Bimmer Claessen (Mount Sinai Hospital, NY, USA) answered, “Previously, many studies had reported a strong association between biomarkers of inflammation such as CRP or white blood cell count and cardiovascular events after PCI. Moreover, the results of the CANTOS trial showed a clear benefit of the anti-inflammatory agent canakinumab (an interleukin-1beta antibody) with regards to lowering recurrent cardiovascular events in patients with an increased baseline hsCRP.” He added, “The ongoing CIRT trial will provide further insights, this was a randomized controlled trial comparing low-dose methotrexate versus placebo in patients with a prior myocardial infarction and either diabetes mellitus or metabolic syndrome. This highly anticipated trial which is powered for a composite endpoint of myocardial infarction, stroke, or cardiovascular death will be presented at the upcoming AHA scientific sessions in Chicago.”
“As this is the first report investigating serial hsCRP measurements, it is too soon to directly translate these results into recommendations for clinical practice. Replication of our data in other datasets and prospective validation in randomized controlled trials is necessary to be able to confidently withhold expensive anti-inflammatory medication from patients with attenuated inflammatory risk and/or recommend more aggressive anti-inflammatory therapy in patients with persistent high residual inflammatory risk.” -Dr. Bimmer Claessen, MD. PhD
Stratification into 4 groups
The retrospective, cohort study looked at patients who underwent PCI between 2009 and 2016 in the prospective PCI registry of Mount Sinai Hospital in New York. The study included 7026 patients who had two or more high sensitive C-reactive protein (hsCRP) measurements at baseline and follow-up with more than 4 weeks apart. Patients were stratified into 4 groups according to their serial hsCRP readings: persistent high RIR (38%), increased RIR (10%), attenuated RIR (15%), and persistent low RIR (37%).
The primary outcome of all-cause mortality at 1 year of follow-up was significantly higher in the persistent high RIR group (2.6%) when compared with the increased RIR, attenuated RIR, and persistent low RIR groups (1%, 0.3%, and 0.7% respectively). Similarly, the secondary outcome of MI occurrence at 1 year of follow-up was higher in the persistent high RIR group (7.5%) when compared to the other three groups (6.4%, 4.6%, and 4.3% respectively). P value was <0.01 for all the previous results and the significance was sustained even after adjusting for diabetes mellitus, acute coronary syndrome, and baseline low-density lipoprotein (LDL).
Dr. Claessen commented on the benefit of using serial hsCRP readings in the study saying, “An important drawback of single CRP measurement for risk prediction is that CRP levels can fluctuate over time depending on several factors. What the current study shows is that measuring multiple CRP values with at least a 4-week interval can help to identify patients who are at highest risk for adverse events. This analysis shows that patients with persistent high residual inflammatory risk are the highest-risk subgroup, who may potentially benefit the most from adjunct anti-inflammatory therapy. Interestingly, it also shows that patients with attenuated inflammatory risk (high hsCRP at the first, but low hsCRP at the second measurement) have a relatively low risk of recurrent adverse events and may therefore not benefit from expensive adjunctive medication.”
Prevalence and subgroup analysis
The prevalence of patients with high RIR in the study was low compared to the trials and registries such as the PROVE-IT and the IMPROVE-IT trials. The authors suggested that the high percentage of patients having hyperlipidemia and arterial hypertension in their registry explained this finding as the treatment for these diseases may have had anti-inflammatory action. In the subgroup analysis, it was found that the prognostic value of persistently high RIR was sustained whether patients had elective PCI or acute coronary syndrome and whether their baseline LDL level was higher or lower than 70 mg/dL. However, the predictive value was found to be stronger in men.
“As this is the first report investigating serial hsCRP measurements, it is too soon to directly translate these results into recommendations for clinical practice. Replication of our data in other datasets and prospective validation in randomized controlled trials is necessary to be able to confidently withhold expensive anti-inflammatory medication from patients with attenuated inflammatory risk and/or recommending more aggressive anti-inflammatory therapy in patients with persistent high residual inflammatory risk,” Dr. Claessen concluded.