Frontiers in nutrition · 2026
Association of serum 25-hydroxyvitamin D and homocysteine "double-risk" status with executive dysfunction in older adults with hypertension.
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Tan Lili, Zhao Linya, Li Hongyan, Zhao Yamin, Chen Yinyin
Аннотация
BACKGROUND: Executive dysfunction is common in adults with hypertension and undermines self-management. Low 25-hydroxyvitamin D [25(OH)D] and elevated homocysteine may damage the endothelium and white matter, while their non-linear dose-response and joint effects on executive dysfunction are unclear.
METHODS: We conducted a single-center, prospective, cross-sectional study of inpatients aged ≥60 years with hypertension (November 2023-July 2024). Exposures were vitamin D deficiency [25(OH)D < 20 ng/mL] and hyperhomocysteinemia (hymocysteine ≥15 μmol/L), combined into a four-level dual-risk variable. Executive function was a composite of four tests. Non-linear associations were estimated with logistic regression using restricted cubic splines. Multiplicative interaction was assessed after adjustment for demographic, clinical, renal, lifestyle, supplementation, and seasonal covariates.
RESULTS: Out of 498 individuals screened, 452 participants were analyzed. Vitamin D deficiency was observed in 49% participants, with hyperhomocysteinemia in 34%, dual-risk in 22%, and executive dysfunction in 38% participants. Non-linear associations were evident for both biomarkers (p_non-linear ≤0.04). Adjusted odds of executive dysfunction were 1.61 (95% CI 1.2-2.2) at 25(OH)D = 15 vs. 30 ng/mL and 1.4 (1.1-2.0) at homocysteine 18 vs. 10 μmol/L. Relative to neither risk, dual-risk had OR 2.1 (1.5-2.9) with multiplicative interaction (p = 0.03) and additive synergy (excess risk due to interaction 0.45, 95% CI 0.06-0.95).
CONCLUSION: In older hypertensive inpatients, lower 25(OH)D and higher homocysteine are non-linearly associated with executive dysfunction, and co-occurrence confers excess risk beyond individual effects. Assessing both biomarkers may enhance risk stratification and guide trials of combined correction.
METHODS: We conducted a single-center, prospective, cross-sectional study of inpatients aged ≥60 years with hypertension (November 2023-July 2024). Exposures were vitamin D deficiency [25(OH)D < 20 ng/mL] and hyperhomocysteinemia (hymocysteine ≥15 μmol/L), combined into a four-level dual-risk variable. Executive function was a composite of four tests. Non-linear associations were estimated with logistic regression using restricted cubic splines. Multiplicative interaction was assessed after adjustment for demographic, clinical, renal, lifestyle, supplementation, and seasonal covariates.
RESULTS: Out of 498 individuals screened, 452 participants were analyzed. Vitamin D deficiency was observed in 49% participants, with hyperhomocysteinemia in 34%, dual-risk in 22%, and executive dysfunction in 38% participants. Non-linear associations were evident for both biomarkers (p_non-linear ≤0.04). Adjusted odds of executive dysfunction were 1.61 (95% CI 1.2-2.2) at 25(OH)D = 15 vs. 30 ng/mL and 1.4 (1.1-2.0) at homocysteine 18 vs. 10 μmol/L. Relative to neither risk, dual-risk had OR 2.1 (1.5-2.9) with multiplicative interaction (p = 0.03) and additive synergy (excess risk due to interaction 0.45, 95% CI 0.06-0.95).
CONCLUSION: In older hypertensive inpatients, lower 25(OH)D and higher homocysteine are non-linearly associated with executive dysfunction, and co-occurrence confers excess risk beyond individual effects. Assessing both biomarkers may enhance risk stratification and guide trials of combined correction.