Study Suggests That Higher Residual Inflammatory Risk Linked to Increased Rates of Ischemic Events in Patients Undergoing Percutaneous Coronary Intervention

A study led by Dr. Paul Guedeney that was published in the Journal of the American College of Cardiology showed that among patients undergoing percutaneous coronary intervention with an LDL of 70 mg/dl or less, a persistently high residual inflammatory risk is associated with an increased risk of major adverse cardiovascular and cerebrovascular events. Potentially targeting the increased residual inflammatory risk could improve outcomes in patients undergoing percutaneous coronary intervention (PCI).

Patients with ischemic heart disease undergoing percutaneous coronary intervention (PCI) are at an increased risk of an ischemic event. There have been many strategies in the past that aimed to improve outcomes in patients undergoing PCI. These included optimizing risk factor control including low-density lipoprotein (LDL) levels and the development of more potent antithrombotic medication. Inflammation has been another potential target. The increased inflammatory activity has been associated with poor prognosis. However, the prevalence and clinical impact of a high inflammatory response in patients with an LDL of less than 70mg/dl is not clear. The authors aimed to characterize the prevalence of persistent residual inflammatory response (RIR) in patients undergoing PCI with controlled cholesterol risk.

All patients undergoing PCI in a tertiary center between January 2009 and December 2016 with a baseline LDL < 70mg/dl and serial high sensitivity C-reactive protein (hsCRP) of at least 2 measurements more than 4 weeks apart were identified. Patients were divided into groups based on their RIR. A high RIR was defined as hsCRP > 2 mg/l. Patients were characterized as persistent low RIR (both the first and second hsCRP were low), attenuated RIR (first hsCRP high and second was low), increased RIR (first low and then high), or persistent high (first high then high hsCRP). The primary endpoint of interest was the presence of major adverse cardiovascular and cerebrovascular accident (MACCE) within 1 year of the second hsCRP. MACCE included death, myocardial infarction, and stroke.

Of the 9,552 patients with a low LDL who underwent PCI between 2009 and 2016, 3,013 (31.5%) had CRP measurements at least 4 weeks apart. A total of 1,225 patients (40.7%) were in the consistently low RIR group, 1,028 (34.1%) were in the persistently high group, and 346 (11.5%) and 414 (13.7%) patients were in the increased and attenuated RIR respectively. The consistently high RIR group had a higher proportion of female patients as well as diabetes, chronic kidney disease, and smoking. The rate of MACCE was highest in the patients with the consistently high RIR group. Compared to those with persistently low RIR, those with a persistently high RIR had the highest risk of a MACCE event (HR 2.10, p <0.001), followed by increased RIR (HR 1.91, p=0.006), and finally, attenuated RIR (HR 1.52, p = 0.08).

The current study demonstrated that a persistent high RIR was observed in one-third of patients undergoing PCI. Additionally, this elevated RIR was associated with an increased risk of a MACCE event. When discussing the results of the study, Dr. Guedeney noted, “The present study brings real-world evidence that even this population remains at high risk of adverse events, despite optimized medical therapy, including statins prescription at discharge in >90% of the patients. Our study further demonstrates that residual inflammatory risk remains prevalent in such a population, with nearly one-half of the patients presenting with hsCRP >2 mg/l at follow-up.” In an editorial published with the study, Dr. Brendan Everett compared the findings of this study with previously reported data. Dr. Everett wrote, “these results confirm and extend 2 previously reported, but important findings: first, residual inflammatory risk is present in approximately one-third of all post-MI patients, even if those patients have been treated with statins and other aggressive LDL-C reduction strategies. Second, residual inflammatory risk is associated with an important and clinically relevant elevation in the risk of MI, stroke, and all-cause mortality. The combination of these 2 factors—the prevalence of the risk marker, and its association with adverse outcome—suggests a problem of broad importance in patients with established coronary artery disease.”