U-Shaped Relationship Between Blood Pressure and All-Cause Mortality in Older Adults: The Shizuoka Study

Objective: Not only high blood pressure (BP) but also low BP was suggested to be associated with all-cause mortality in older adults. However, the actual mechanism responsible for the association between low BP and mortality has not been identified. This study aimed to investigate a possible confounding of antihypertensive drug use, potential comorbidities, and functional disability, as well as random error in BP measurement, in the association between low BP and all-cause mortality. A possibility of reverse causation (i.e., lower BP was caused by cardiovascular frailty at the end of life) was also investigated. Design and method: We use the Kokuho Database in a local government, which is a prefecture-wide large dataset including data on annual health checkup and health and care insurance claims. This longitudinal observational study analyzed 337,988 individuals aged ≥ 65 (mean age: 73.5) years. The earliest day of participation in the annual health checkup during the study period from 2012 to 2020 was defined as baseline. Data on comorbidities, prescribed antihypertensive medications, functional disability levels, and incidence of stroke and all-cause mortality were obtained from the insurance claims database. Results: During a mean follow-up period of 5.3 years, there were 27,497 cases of all-cause mortality and 11,090 cases of stroke. A U-shaped association was observed between systolic BP and all-cause mortality in participants aged ≥ 75 years. The hazard ratio of systolic BP <110 mmHg for all-cause mortality was 1.14 (95% confidence interval: 1.07–1.21, P < 0.001). Meanwhile, the hazard ratio of BP ≥ 150 mmHg was 1.16. The U-shaped association remained significant in the subanalyses of individuals without severe comorbidities, antihypertensive drug use, or functional disability. Similar results were also observed in the analysis excluding early-mortality cases within 3 years after the baseline, as well as in the analysis using the average systolic BP measured during at least two different occasions within a 3-year period as a baseline value. In contrast, stroke risk increased linearly with increasing BP. Conclusions: Low BP was associated with all-cause mortality in older adults. The U-shaped association may not be attributed to the previously suggested factors.