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Significance of Persistent Inflammation in Patients With Chronic Coronary Syndrome: Insights From the REAL-CAD Study
Hiroshi Iwata1, Katsumi Miyauchi1, Ryo Naito1
1Department of Cardiovascular Biology and Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan.
Insights
Persistent low-grade inflammation, indicated by high-sensitivity C-reactive protein (hs-CRP), is linked to worse outcomes in chronic coronary syndrome (CCS) patients. Addressing residual inflammatory risk is crucial for improving prognosis in CCS.
Area of Science:
- Cardiology
- Inflammation Research
- Clinical Trials
Background:
- The prognostic significance of persistent low-grade inflammation in chronic coronary syndrome (CCS) remains understudied.
- The REAL-CAD study previously established the efficacy of higher-intensity pitavastatin in Japanese CCS patients.
Purpose of the Study:
- To investigate the prognostic impact of persistent low-grade inflammation, measured by high-sensitivity C-reactive protein (hs-CRP), in patients with CCS.
- To analyze the association between hs-CRP levels over time and major adverse cardiovascular events.
Main Methods:
- A subanalysis of 10,460 patients from the REAL-CAD study with available hs-CRP data at baseline and 6 months.
- Patients were categorized into four groups based on hs-CRP levels: persistently low, elevated, reduced, and persistently high.
- The primary endpoint was a composite of cardiovascular mortality, myocardial infarction, stroke, and unstable angina hospitalization.
Main Results:
- Persistently high hs-CRP levels were significantly associated with an increased risk of the primary endpoint compared to persistently low levels (adjusted HR: 1.48, 95% CI: 1.18-1.89).
- No significant increase in risk was observed for patients with elevated or reduced hs-CRP levels.
Conclusions:
- Persistent low-grade inflammation is a significant predictor of poor cardiovascular outcomes in CCS patients.
- These findings highlight the importance of managing residual inflammatory risk in CCS management.
Background:
The prognostic implications of persistent low-grade inflammation in patients with chronic coronary syndrome (CCS) are underexplored. The REAL-CAD (Randomized Evaluation of Aggressive or Moderate Lipid Lowering Therapy with Pitavastatin in Coronary Artery Disease) study demonstrated the benefit of higher intensity pitavastatin in Japanese patients with CCS.
Objectives:
This prespecified subanalysis of the REAL-CAD study aimed to assess the prognostic effect of the persistent low-grade inflammation represented by high-sensitivity C-reactive protein (hs-CRP) in CCS patients.
Methods:
The present analysis involved patients without events until 6 months after randomization and whose hs-CRP levels were available at baseline and 6 months (n = 10,460). The primary endpoint was the composite of cardiovascular mortality, myocardial infarction, stroke, and unstable angina hospitalization. Landmark analyses evaluated the prognostic impact of continuous inflammation in 4 groups based on the median levels of hs-CRP (0.5 mg/L for both) at baseline and 6 months. The 4 groups included patient with persistently low, elevated (increased), reduced, and persistently high hs-CRP.
Results:
Adjusted Cox proportional hazard analyses demonstrated an increased risk of the primary endpoint in the group with persistently high hs-CRP when compared to the group with persistently low hs-CRP as a reference (adjusted HR: 1.48, 95% CI: 1.18-1.89; P = 0.001), but with a similar risk in the group with elevated (HR: 1.07, 95% CI: 0.77-1.49, P = 0.68) and reduced (HR: 0.92; 95% CI: 0.66-1.27; P = 0.60) hs-CRP.
Conclusions:
The study shows that persistent low-grade inflammation is associated with poor outcomes and underscores the need to address residual inflammatory risk in CCS patients. (Randomized Evaluation of Aggressive or Moderate Lipid Lowering Therapy With Pitavastatin in Coronary Artery Disease [REAL-CAD]; NCT01042730).
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