Significance of Residual Inflammatory Risk and Persistent Inflammation in Patients with Myocardial Infarction with Nonobstructive Coronary Arteries

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Background: Inflammation as assessed by high-sensitivity C-reactive protein (hs-CRP) predicts cardiovascular outcomes independently of low-density lipoprotein cholesterol (LDL-C) levels even in statin-treated patients with coronary artery disease. However, data regarding implications of residual inflammatory risk in patients with myocardial infarction with nonobstructive coronary arteries (MINOCA) are lacking. Methods: The present single-center cohort study prospectively enrolled 1062 patients with MINOCA stratified by the baseline hs-CRP (≥2 vs <2 mg/L) and LDL-C (≥70 vs <70 mg/dL). Change patterns of hs-CRP were identified in 792 patients with available hs-CRP at baseline and within 6-12 months after index MI. The primary endpoint was major adverse cardiovascular events (MACE), a composite of death, nonfatal MI, stroke, revascularization, and hospitalization for unstable angina or heart failure. Results: During the median follow-up of 41.7 months, patients with isolated residual inflammatory risk had the highest rate of MACE, followed by patients with combined cholesterol and inflammatory risk. At multivariate Cox model, residual inflammatory risk but not cholesterol risk was associated with an increased risk of MACE compared to those with no residual risk [hazard ratio (HR) 1.51; 95% confidence interval (CI): 1.17-1.97, p=0.002]. The prognostic impact of hs-CRP ≥2mg/L remained significant in subgroup analysis, and particularly, in patients with well-managed LDL-C levels. Patients with persistently higher hs-CRP had a significantly higher risk of MACE than those with persistently low hs-CRP (HR 1.28; 95% CI: 1.09-1.50, p=0.020). Conclusion: Residual inflammation but not cholesterol risk drives poorer outcomes after MINOCA in the statin era, highlighting inflammation as a pivotal risk predictor and the necessity for anti-inflammatory strategies alongside LDL-C lowering.

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