Urinary albumin-to-creatinine ratio and the risk of first stroke in Chinese hypertensive patients treated with angiotensin-converting enzyme inhibitors

We aimed to evaluate the relationship of the albumin-to-creatinine ratio (ACR) with the risk of first stroke and examine possible effect modifiers in hypertensive patients. A total of 11,632 hypertensive participants with urinary ACR measurements and without a history of stroke from the China Stroke Primary Prevention Trial (CSPPT) were included in this analysis. The primary outcome was first stroke. Over a median follow-up of 4.4 years, 728 first strokes were identified, of which 633 were ischemic, 89 were hemorrhagic, and 6 were uncertain types. Overall, there was a significant positive association between natural log-transformed ACR and the risk of first stroke (HR, 1.11; 95% CI: 1.03-1.20) and first ischemic stroke (HR, 1.12; 95% CI: 1.03-1.22). Consistently, participants with ACR ≥ 10 mg/g had a significantly higher risk of first stroke (HR, 1.26; 95% CI: 1.06-1.50) and first ischemic stroke (HR, 1.33; 95% CI: 1.10-1.59) than those with ACR < 10 mg/g. Moreover, the association of ACR with first stroke was significantly stronger in participants with higher total homocysteine (tHcy) levels (<10 versus ≥ 10 μmol/L; P for interaction = 0.044). However, there was no significant association between ACR and first hemorrhagic stroke (per natural log [ACR] increment: HR, 1.02; 95% CI: 0.82-1.27). In summary, hypertensive patients with ACR ≥ 10 mg/g had a significantly increased risk of first stroke or first ischemic stroke. This positive association was more pronounced among participants with higher tHcy levels.