Data Management And Sharing System of China National Clinical Research Center for Neurological Diseases
The Contribution of Inflammation to Stroke Recurrence Attenuates at Low LDL-C Levels
First author：Xing Zhang,Wei Lv
Corresponding author：Yongjun Wang
essential_information
- Person in charge：Xing Zhang,Wei Lv
- Data Sources： CNSR-Ⅲ
- Number of papers：CNSR-Ⅲ20200171
- Published time：2022-01-09
2022-01-09
Published articles
Journal：Journal of Atherosclerosis and Thrombosis
Publication type: Article
IF(IF): 4.9
PMID: 35013023 Link To Pubmed Full text Download
Background And Purpose
Elevated LDL-C is a well-established risk factor for atherosclerosis. Data from SPARCL (Stroke Prevention by Aggressive Reduction in Cholesterol Levels) and TST (Treat Stroke to Target) trail have demonstrated that intensively reduced LDL-C concentration to the target level (<70 mg/L) could effectively reduce the risk of stroke recurrence. However, studies showed that even though LDL-C is controlled to achieve the target level after contemporary lipid lowering therapy, residual risks still exist. The Canakinumab Anti-inflammatory Thrombosis Outcome Study (CANTOS) establishes the cornerstone status of residual inflammation risk in cardiovascular diseases, which showed that anti-inflammatory therapy with canakinumab reduced hsCRP levels, and then effectively reduced recurrent cardiovascular events by 27%, indicating that residual inflammation was a modifiable risk factor and proposed a potential treatment target for patients with cardiovascular disease. To our knowledge, the elevated hsCRP levels is always related positively with LDL-C levels. And other studies have confirmed that lipoprotein metabolism disorder could induce inflammatory and immune response in the formation and progress of atherosclerosis. The question is, if LDL-C concentration is reduced to an extremely low level, the inflammatory level will also decrease, then the contribution of inflammation to cardiovascular event will be attenuated at the lower level of LDL-C. Therefore, we hypothesis that the influence of inflammation on risk of cardiovascular decreases as LDL-C levels decline. This study aims to investigated this issue among patients with IS/TIA in Chinese population based on CNSR III.
Method
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.
Conclusion
For IS/TIA patients, the contribution of inflammation to stroke recurrence seems to be attenuated at a low level of LDL-C.
Main 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).