Interactive effects of vitamin D status and visit-to-visit systolic blood pressure variability on 12-month cognition and mild cognitive impairment in older adults with hypertension

BACKGROUND: Visit-to-visit systolic blood pressure variability (BPV) has been linked to cognitive decline, but inter-individual susceptibility may depend on modifiable factors such as vitamin D status. We investigated whether baseline serum 25-hydroxyvitamin D [25(OH)D] modifies the association between systolic BPV and 12-month cognition among older adults with hypertension. METHODS: In this single-center prospective cohort, participants were recruited from May 2023 to June 2024 and followed for 12 months, adults aged ≥ 65 years with hypertension underwent baseline 25(OH)D measurement and Montreal Cognitive Assessment (MoCA) at baseline and Month 12. BPV was calculated from clinic SBP values during Months 0-10 (≥ 6 visits required). Average real variability of SBP (ARV-SBP) was the primary BPV metric; standard deviation (SD-SBP), coefficient of variation (CV-SBP), variability independent of mean (VIM-SBP), and range-SBP were examined in sensitivity analyses. Average real variability of SBP (ARV-SBP) was the primary BPV metric. The primary analysis used ANCOVA-style multivariable linear regression for Month 12 MoCA including ARV-SBP (per 1 SD), 25(OH)D (per 10 ng/mL, centered), and their interaction, adjusting for baseline MoCA and prespecified covariates. A screening-based, algorithm-defined MCI status at Month 12 was analyzed using modified Poisson regression with robust standard errors. RESULTS: Among 176 participants (mean age 73.1 years), 73 (41.5%) had low vitamin D status [25(OH)D < 20 ng/mL] and 48 (27.3%) met algorithm-defined MCI status at Month 12. Higher ARV-SBP was associated with lower Month 12 MoCA (β=-0.22, 95% CI - 0.37 to - 0.07 β), and 25(OH)D significantly modified this association (interaction β = 0.18, 95% CI 0.05 to 0.32; p = 0.01 β), indicating attenuation of BPV-related cognitive disadvantage at higher vitamin D levels. The interaction remained directionally consistent across SD-SBP, CV-SBP, VIM-SBP, and range-SBP sensitivity models (all nominal p ≤ 0.04 ; FDR q ≤ 0.04 ). In joint-exposure analysis, low vitamin D status plus high BPV was associated with a higher probability of meeting algorithm-defined MCI status versus 25(OH)D ≥ 20 ng/mL with low BPV (adjusted RR = 4.14, 95% CI 1.93 to 8.90), while additive interaction was suggestive but imprecise (RERI = 1.94, 95% CI - 0.10 to 6.03). CONCLUSIONS: Baseline 25(OH)D was associated with heterogeneity in the observed association between clinic visit-to-visit systolic BPV and 12-month cognition in adults aged ≥ 65 years with hypertension. These findings support attention to BP stability and low vitamin D status as a potential marker of cognitive vulnerability in older hypertensive outpatients, while causal inference and supplementation effects require confirmation.