Plasma Vitamin E and the Risk of First Stroke in Hypertensive Patients: A Nested Case-Control Study

Abstract

Background: The association between plasma vitamin E levels and first stroke risk in men and women remains unclear. Objective: We aimed to examine the prospective association between plasma vitamin E and first stroke, and evaluate the effect modifiers for the association, among hypertensive patients. Design: The study sample was drawn from the China Stroke Primary Prevention Trial (CSPPT), which randomized a total of 20,702 hypertensive patients to a double-blind, daily treatment with either 10 mg enalapril and 0.8 mg folic acid or 10 mg enalapril alone. This nested case-control study, including 618 first stroke cases and 618 controls matched for age, sex, treatment group, and study site, was conducted after the completion of the CSPPT. Results: The median follow-up duration was 4.5 years. Among men, a significantly higher risk of first stroke (adjusted OR, 1.67; 95%CI: 1.01, 2.77) was found for those with plasma vitamin E ≥7.1 μg/mL (≥quartile 1) compared with those with plasma vitamin E < 7.1 μg/mL. Subgroup analyses further showed that the association between vitamin E (≥7.1 vs. <7.1 μg/mL) and first stroke in men was significantly stronger in non-drinkers (adjusted OR, 2.64; 95%CI: 1.41, 4.96), compared to current drinkers (adjusted OR, 0.84; 95% CI: 0.43, 1.66, P-interaction = 0.008). However, there was no significant association between plasma vitamin E and first stroke in women (P-interaction between sex and plasma vitamin E = 0.048). Conclusions: Among Chinese hypertensive patients, there was a statistically significant positive association between baseline plasma vitamin E and the risk of first stroke in men, but not in women. Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT00794885, Identifier: NCT00794885.

Keywords: first ischemic stroke; first stroke; hypertensive males; sex; vitamin E.

Figure 1

Flow chart of the study participants: A nested case control design based on the China Stroke Primary Prevention Trial (CSPPT).

Figure 2

Association between plasma vitamin E (< quartile 1 vs. ≥quartile 1) and risk of first total stroke among males in various subgroups. Each subgroup analysis adjusted, if not stratified, for age, treatment group, study site, body mass index (BMI), smoking status, alcohol drinking, systolic blood pressure at baseline (SBP), fasting blood glucose, total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), total homocysteine (tHcy), folate, as well as estimated glomerular filtration rate (eGFR) at baseline.