The Contribution of Inflammation to Stroke Recurrence Attenuates at Low LDL-C Levels

Aims: Residual inflammation risk refers to inflammation that still increases the risk of cardiovascular disease after the level of low-density lipoprotein cholesterol (LDL-C) reached the target (＜70 mg/dL). However, whether inflammation is still an important issue even if very low LDL-C levels have been achieved remains unclear. This study aimed to investigate the contribution of inflammation to stroke recurrence on different LDL-C levels following ischemic stroke (IS) or transient ischemic attack (TIA).

Methods: A total of 10499 IS/TIA patients whose LDL-C and high-sensitivity C-reactive protein (hsCRP) were measured were selected from the Third China National Stroke Registry. The cutoff values were set to 25, 35, 45, 55, 70, and 100 mg/dL for LDL-C, whereas the threshold values of hsCRP and interleukin-6 (IL-6) were 2 mg/L and 1.65 ng/L, respectively. Based on each group of LDL-C, Cox regressions were conducted to investigate the associations between inflammation and recurrent stroke within 1 year.

Results: The associations between baseline hsCRP levels and stroke recurrence were non-significant in groups with LDL-C ＜55 mg/dL (P＞0.05). After stratification by baseline LDL-C of 55 mg/dL, hsCRP ≥ 2 mg/L (10.9% versus 7.5%, P＜0.0001) and IL-6 ≥ 1.65 ng/L (9.8% versus 7.4%, P=0.0002) were found to be related to a high incidence of recurrent IS among patients with LDL-C ≥ 55 mg/dL; however, no associations were observed among patients with LDL-C ＜55 mg/dL. Compared with low inflammation (both hsCRP ＜2 mg/L and IL-6 ＜1.65 ng/L), high inflammation (both hsCRP ≥ 2 mg/L and IL-6 ≥ 1.65 ng/L) was significantly associated with stroke recurrence when LDL-C ≥ 55 mg/dL (adjusted HR 1.38, 95% CI 1.10-1.74), whereas this association was not observed when LDL-C ＜55 mg/dL (adjusted HR, 0.72; 95% CI, 0.41-1.25).

Conclusion: For IS/TIA patients, the contribution of inflammation to stroke recurrence seems to be attenuated at a low level of LDL-C.