Plasma Soluble Angiotensin-Converting Enzyme 2 and Risk of Recurrent Stroke: A Nested Case-Control Analysis

Abstract

Introduction: The angiotensin-converting enzyme 2 (ACE-2) and its shedding product (soluble ACE-2 [sACE-2]) are implicated in adverse cardiovascular outcomes. However, the relationship between sACE-2 and stroke recurrence is unknown. Herein, we examined the relationship of sACE-2 with stroke recurrence in patients with ischemic stroke or transient ischemic attack. Methods: Data were obtained from the Third China National Stroke Registry (CNSR-III). Eligible cases consisted of 494 patients who developed recurrent stroke within 1-year follow-up, and 494 controls were selected using age- and sex-matched with a 1:1 case-control ratio. Conditional logistic regressions were used to evaluate the association between sACE-2 and recurrent stroke. The main outcomes were recurrent stroke within 1 year. Results: Among 988 patients included in this study, the median (interquartile range) of sACE-2 was 25.17 (12.29–45.56) ng/mL. After adjustment for conventional confounding factors, the odds ratio (OR) with 95% confidence interval (CI) in the highest quartile versus the lowest quartile was 1.68 (1.12–2.53) for recurrent stroke within 1-year follow-up. Subgroup analysis showed that the association between elevated plasma level of sACE-2 and stroke recurrence was significant in patients with higher systemic inflammation, as indicated by high-sensitivity C-reactive protein ≥ 2 mg/L (adjusted OR: 2.33 [95% CI, 1.15–4.72]) and neutrophil counts ≥ median (adjusted OR: 2.66 [95% CI, 1.35–5.23]) but not significant in patients with lower systemic inflammation. Discussion/Conclusion: Elevated plasma sACE-2 concentration was associated with increased risk of recurrent stroke.