image: Take home figure: Concept of residual inflammatory risk and the main findings of this study. High high sensitive C-reactive protein is defined as >2 mg/L. aAdjusted for age, gender, body mass index, acute coronary syndrome, diabetes mellitus, hypertension, chronic kidney disease, previous coronary artery bypass graft, and baseline low-density lipoprotein cholesterol. Red hazard ratio indicates a P-value <0.01. MACE, major adverse cardiovascular events, composite of death, MI, and CVA; MACEþ, MACE with any revascularization; MI, myocardial infarction. view more
Credit: Roxana Mehran, Mount Sinai Medical Center, New York, USA
Patients who have persistently high levels of inflammation following percutaneous coronary intervention (PCI) for coronary artery disease are significantly more likely to die from any cause or to have a heart attack within a year, according to a study of 7,026 patients published in the European Heart Journal [1].
Residual inflammatory risk (RIR) refers to the risk of further heart and blood vessel problems caused by vascular inflammation in patients with known coronary artery disease. A biological marker - high sensitivity C-reactive protein (hsCRP) - is used as an indicator of the level of risk. Until now it has not been known what proportion of patients treated with PCI to widen blocked arteries [2] have persistent high RIR, and what effect it might have on patient outcomes.
In the first study to investigate the prevalence of persistent high RIR after PCI, researchers led by Professor Roxana Mehran, from the Mount Sinai Medical Center, New York, USA, looked at data from patients who had received PCI at Mount Sinai Hospital between 2009 and 2016. They included all patients who had two measurements of hsCRP taken at the time of the PCI and then again at least four weeks later.
Patients were stratified into four groups according to their RIR: high RIR was defined as having levels of hsCRP of more than 2mg per litre of blood. If both measurements were high, then they were considered to have persistent high RIR; patients with a high first measurement, but then a low second measurement were considered to have attenuated RIR; those with a low and then high measurement had an increased RIR; and those whose measurements were both low had a low persistent low RIR.
Of the 7,026 patients, 2,654 (38%) had persistent high RIR, 719 (10%) had increased RIR, 1,088 (15%) had attenuated RIR, and 2,565 (37%) had persistent low RIR. One year after PCI, death from any cause had occurred in 2.6% of persistent high RIR patients, 1% of increased RIR patients, 0.3% of attenuated RIR patients and 0.7% of persistent low RIR patients. Heart attacks (myocardial infarction) occurred in 7.5%, 6.4%, 4.6% and 4.3% of the patients, respectively.
After adjusting for various factors that could affect the results, such as age, gender, body mass index, diabetes, high blood pressure and other conditions, the researchers found that compared to patients with persistent low RIR, persistent high RIR patients were more than three times more likely to die within one year from any cause and were 1.6 times as likely to have a heart attack.
Professor Mehran said: "Our results show that in patients for whom serial hsCRP measurements were available, more than a third of PCI patients had persistent high residual inflammatory risk. Moreover, cardiologists are clearly not evaluating residual inflammatory status in all patients after PCI. This should be considered, as we find it is associated with a higher risk of dying from any cause or suffering a heart attack within one year of PCI. Additionally, it is of interest because there are treatment strategies emerging aimed at lowering residual inflammatory risk."
She pointed to the results of a recent trial, CANTOS (Canakinumab Anti-inflammatory Thrombosis Outcomes Study), that found that a monoclonal antibody, canakinumb, which reduces hsCRP, significantly reduced deaths from cardiovascular disease, stroke, myocardial infarction, and reduced the incidence of major adverse cardiac events in patients who had a history of heart attacks and elevated hsCRP.
"The results of the CANTOS study were astonishing. Not only a reduction in hsCRP was found, but more importantly a significant reduction in heart attack, stroke or cardiovascular death was found in patients who took canakinumab. It is clearly important to identify the patients at highest risk who can benefit from the therapy, and to evaluate this in a prospective study. I do believe that we need data from randomised controlled trials to confirm our observational findings in patients undergoing PCI and with persistent high residual inflammatory risk.
"Our study emphasises that treating patients with coronary artery disease is not 'one-size-fits-all'. Patients fall into different risk categories and it's the clinicians' task to evaluate all residual risks after PCI. I hope that in the future we will be able to treat all patients according to their own individual risk profile."
Professor Paul Ridker, Director of the Center for Cardiovascular Disease Prevention at the Brigham and Women's Hospital, Boston, USA, who is an expert on inflammation in heart disease, developing the clinical application of hsCRP testing to evaluate cardiovascular risk and leading the CANTOS trial, has written an accompanying Viewpoint article with European colleagues, which is published today (Monday) [3]. He writes that while European clinicians "enthusiastically measure cholesterol and blood pressure in virtually all of their patients, surprisingly few measure high sensitivity C-reactive protein (hsCRP), a validated measure of cardiovascular inflammation".
He writes that the current study provides yet more evidence of the importance of measuring hsCRP to prevent further cardiovascular problems, and concludes: "Physicians can only address the biologic processes they measure. Without assessment of LDL cholesterol, it is impossible to effectively identify and manage hyperlipidaemia. Without knowledge of systolic and diastolic blood pressure, it is impossible to effectively identify and manage hypertension. Without measuring hsCRP, it is unclear how we will effectively identify and manage residual inflammatory risk. while today the management of the residual inflammatory risk involves more aggressive and guideline-based treatment of the currently known risk factors, the introduction of effective anti-inflammatory drugs in the near future will provide even better control of this residual risk."
Limitations of Prof Mehran's study include that it is observational; however, the hsCRP measurements were collected at the time of PCI and during follow-up, but were evaluated retrospectively rather than in a standardised prospective way.
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Notes:
[1] "Residual inflammatory risk and the impact on clinical outcomes in patients after percutaneous coronary interventions", by Deborah N. Kalkman et al. European Heart Journal. doi:10.1093/eurheartj/ehy633
[2] Percutaneous Coronary Intervention (PCI) is a non-surgical procedure to open narrowed arteries that supply blood to the heart. It is performed by inserting a catheter through the skin in the groin or arm into the artery.
[3] "Has the time finally come to universally measure hsCRP in primary and secondary cardiovascular prevention?", by Paul M. Ridker, Wolfgang Koenig, John J. Kastelein, François Mach and Thomas Lüscher. European Heart Journal. doi:10.1093/eurheartj/ehy723
Journal
European Heart Journal