Hs-CRP modifies the impact of stress hyperglycemia ratio on long-term outcomes in patients with acute coronary syndrome

Abstract

Abstract Background In recent years, studies have demonstrated the promising predictive value of stress hyperglycemia ratio (SHR) for adverse outcomes in patients with acute coronary syndrome (ACS). Nevertheless, knowledge regarding the effects of inflammation on the risks associated with SHR remains limited. Considering the potential interplay, we hypothesize that the well-recognized biomarker reflecting residual inflammation, high-sensitivity C-reactive protein (hs-CRP), may exert an influence on SHR-related cardiovascular risks. Purpose The objective of this study was to investigate the association between hs-CRP level and SHR-related long-term adverse events in ACS patients. Methods Among 10,724 consecutive patients who underwent percutaneous intervention treatment throughout the year 2013, 6149 ACS patients were eventually enrolled. SHR was calculated employing the formula: SHR = admission blood glucose (ABG) / [1.59 x HbA1c (%) – 2.59]. Based on their levels of hs-CRP, patients were stratified into two groups, with the cut-off set at 2 mg/L. The primary endpoint was defined as all-cause mortality, and the secondary endpoint was the major adverse cardiac and cerebrovascular events (MACCE), consisting of all-cause death, non-fatal myocardial infarction, coronary revascularization, and ischemic stroke. Results 238 (3.7%) all-cause mortality and 1275 (20.0%) MACCE occurred during the 5-year follow-up. The average age of the overall cohort was 58.39 ± 10.38 years, and 4723 (76.8%) were male. After adjusting for the potential confounders, multivariable Cox regression revealed a significant correlation between hs-CRP level and SHR for all-cause mortality (P for interaction = 0.009), and there were diverse associations between SHR and long-term risks depending on the levels of hs-CRP: With hs-CRP < 2mg/L, there was no significant risk of all-cause mortality at any SHR quantiles, while the lowest SHR quantile showed a 1.321-fold increased risk of MACCE [Hazard Ratio (HR): 1.321, 95% confidence interval (CI) 1.034-1.688, P = 0.026]. Conversely, with hs-CRP ≥ 2mg/L, significant association was observed between SHR and all-cause mortality (all P < 0.05). Notably, the highest SHR quantile exhibited the greatest risk for both all-cause mortality (HR: 4.030, 95% CI 1.778-9.134, P < 0.001) and MACCE (HR: 1.299, 95% CI 1.010-1.672, P = 0.042). Conclusions This large-scale real-world study was the first to report that the pattern of SHR-associated long-term cardiovascular risks in ACS patients was modified by the levels of hs-CRP, suggesting a potential interaction between inflammation and stress hyperglycemia that contributes to poor prognosis. When applying risk stratification, both factors should be comprehensively considered, and patients exhibiting high SHR along with concomitantly elevated hs-CRP may merit more rigorous risk management.Figure 1.Multivariable COX regression