Association between Plasma Homocysteine Concentrations and the First Ischemic Stroke in Hypertensive Patients with Obstructive Sleep Apnea: A 7-Year Retrospective Cohort Study from China

PURPOSE: This study was aimed at investigating the association between baseline plasma homocysteine (Hcy) concentrations and the risk of the first ischemic stroke (IS) and at investigating any possible influential modifying factors in hypertensive patients with obstructive sleep apnea (OSA). METHODS: Cox proportional hazards regression was employed to investigate the relationship between plasma Hcy concentration and the first IS. A generalized additive model was applied to determine the nonlinear relationship. In addition, we conducted subgroup analysis. RESULTS: A total of 2350 hypertensive patients with OSA without a history of IS were enrolled in this study. At a median follow-up of 7.15 years, we identified 93 cases of the first IS. After adjusting for potential confounding, the findings revealed that plasma Hcy concentration was strongly and positively associated with the occurrence of the first IS (per SD increment; HR = 1.37, 95% CI: 1.30-1.44). A nonlinear relationship was found between plasma Hcy concentration and the risk of developing the first IS with inflection points for plasma Hcy of 5 μmol/L. In stratified analysis, a greater positive correlation was found between baseline plasma Hcy concentrations and new-onset IS in patients with DBP ≥ 90 mmHg (per SD increment; HR = 1.48, 95% CI: 1.33-1.65 vs. <90 mmHg: HR = 1.20, 95% CI: 1.02-1.42; P‐interaction = 0.04) and BMI ≥ 24 and <28 kg/m(2) (per SD increment; HR = 1.46, 95% CI: 1.26-1.70 vs. <24 kg/m(2): HR = 1.13, 95% CI: 0.95-1.33 vs. ≥28 kg/m(2): HR = 1.46, 95% CI: 1.25-1.70; P‐interaction = 0.03). CONCLUSION: Elevated plasma Hcy concentrations are independently associated with the risk of the first IS in hypertensive patients with OSA. Plasma Hcy concentrations ≥ 5 μmol/L surely increased the risk of the first IS in hypertensive patients with OSA.