Visit-to-visit blood pressure variability and dementia risk after considering antihypertensive treatment: real-world data from the Japanese National Health Insurance

Michihiro Satoh; Hiroki Nobayashi; Shingo Nakayama; Yutaro Iwabe; Takahito Yagihashi; Seiya Izumi; Takahisa Murakami; Yuya Suzuki; Maya Toyama; Tomoko Muroya; Takayoshi Ohkubo; Hirohito Metoki

doi:10.1038/s41440-025-02451-1

Visit-to-visit blood pressure variability and dementia risk after considering antihypertensive treatment: real-world data from the Japanese National Health Insurance

Hypertens Res. 2025 Nov 10. doi: 10.1038/s41440-025-02451-1. Online ahead of print.

Authors

Michihiro Satoh^{1

2

3}, Hiroki Nobayashi^{4

5}, Shingo Nakayama^{4

6}, Yutaro Iwabe^{4

7}, Takahito Yagihashi^{4

8}, Seiya Izumi^{4

9}, Takahisa Murakami^{4

10

11}, Yuya Suzuki^{4

12}, Maya Toyama^{4

13}, Tomoko Muroya^{4

14

15}, Takayoshi Ohkubo^{16

17}, Hirohito Metoki^{4

10

17}

Affiliations

¹ Division of Public Health, Hygiene and Epidemiology, Faculty of Medicine, Tohoku Medical and Pharmaceutical University, Sendai, Japan. satoh.mchr@tohoku-mpu.ac.jp.
² Department of Preventive Medicine and Epidemiology, Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan. satoh.mchr@tohoku-mpu.ac.jp.
³ Department of Pharmacy, Tohoku Medical and Pharmaceutical University Hospital, Sendai, Japan. satoh.mchr@tohoku-mpu.ac.jp.
⁴ Division of Public Health, Hygiene and Epidemiology, Faculty of Medicine, Tohoku Medical and Pharmaceutical University, Sendai, Japan.
⁵ Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan.
⁶ Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
⁷ Center for Clinical Research Promotion and Development, Tohoku Medical and Pharmaceutical University Hospital, Sendai, Japan.
⁸ Department of Neurology, Faculty of Medicine, Tohoku Medical and Pharmaceutical University, Sendai, Japan.
⁹ Department of Obstetrics and Gynecology, Tohoku University Graduate School of Medicine, Sendai, Japan.
¹⁰ Department of Preventive Medicine and Epidemiology, Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan.
¹¹ Division of Aging and Geriatric Dentistry, Department of Rehabilitation Dentistry, Tohoku University Graduate School of Dentistry, Sendai, Japan.
¹² Division of Nephrology and Hypertension, Tohoku Medical and Pharmaceutical University, Sendai, Japan.
¹³ Department of Nephrology, Self-Defense Forces Sendai Hospital, Sendai, Japan.
¹⁴ Division of Internal Medicine, Izumi Hospital, Sendai, Japan.
¹⁵ Nanatsumori Family Clinic, Miyagi, Japan.
¹⁶ Department of Hygiene and Public Health, Teikyo University School of Medicine, Tokyo, Japan.
¹⁷ Tohoku Institute for the Management of Blood Pressure, Sendai, Japan.

PMID: 41214329
DOI: 10.1038/s41440-025-02451-1

Abstract

This retrospective cohort study evaluated the association between visit-to-visit blood pressure (BP) variability and dementia risk, considering antihypertensive drug classes and medication adherence using Japanese National Health Insurance data (2015-2023) of 301,448 participants (age: 66.6 years, male: 38.6%). Visit-to-visit systolic BP (SBP) variability was assessed using the coefficient of variation (CV) from five annual health check-ups. The outcome was antidementia drug initiation as a proxy for dementia diagnosis and was analyzed using Fine-Gray models, with death as the competing outcome. For participants untreated/treated with antihypertensive medication, 366/298 initiated antidementia drugs during 2.20 ± 1.19/2.11 ± 1.19 years of follow-up, respectively. The highest SBP-CV sextile was associated with dementia risk regardless of treatment status: hazard ratio of the 6^th sextile (SBP-CV ≥ 9.83%) vs. 1^st-5^th sextiles was 1.50 (95% confidence interval [CI]: 1.17-1.92) for untreated participants, while for treated participants, the hazard ratio of the 6^th sextile (SBP-CV ≥ 10.67%) was 1.43 (95%CI: 1.09-1.89) after further adjusting for antihypertensive drug classes and medication adherence assessed by medication possession rate. In the stratification analyses by baseline characteristics, only HbA1c in treated participants demonstrated a significant interaction with SBP-CV for dementia risk; this association was pronounced among treated participants with HbA1c ≥ 6.5% (interaction P = 0.024). No significant interactions were observed among antihypertensive drugs, poor adherence, and SBP-CV in relation to dementia risk. High visit-to-visit BP variability, indicated by a CV of approximately ≥10%, is associated with dementia, regardless of treatment status. In the treated participants, this association persisted even after accounting for antihypertensive drug classes and medication adherence.

Keywords: Antihypertensive treatment; Blood pressure variability; Dementia; Digital hypertension; Epidemiology.