What is the clinical evidence from this study?

Study design: Cohort. Population: Hypertension and Dementia (n=5646). Intervention: Mid-adulthood hypertension vs. Normotension. Primary outcome: Dementia incidence (HR 1.65, 95% CI 1.25-2.18).

October 5, 2017

Female sex, early-onset hypertension, and risk of dementia

Key Result

Mid-adulthood hypertension increased the risk of dementia by 65% (HR 1.65) in women compared to normotensive women, with no increased risk observed in men.

Study Design

Type

Cohort (n=5,646)

Multicenter

Yes

Structured PICO

Does early-adulthood and mid-adulthood hypertension increase the risk of dementia in men and women?

Population

5,646 members of the Kaiser Permanente Northern California integrated health care delivery system with clinical examinations and health survey data from 1964-1973 (mean age 32.7 years) and 1978-1985 (mean age 44.3 years), who were members as of January 1, 1996.

Intervention

Hypertension in early adulthood (mean age 32.7) and mid-adulthood (mean age 44.3), and onset of hypertension between these periods.

Comparator

Stable normotensive blood pressure.

Outcome

Dementia incidence from January 1, 1996, to September 30, 2015, identified from electronic medical records using ICD-9 codes.hard clinical

Mid-adulthood hypertension and its onset are associated with a significantly increased risk of dementia in women, but not in men, highlighting important sex differences in the timing of dementia risk factors.

Main Result

Effect estimate: HR 1.65 (95% CI 1.25-2.18)

Limitations

Lack of information on type and dose of antihypertensive medication used
Developments in screening protocols and antihypertensive medications since 1964 limit generalizability to current middle-aged cohorts
Lack of neuroimaging or pathology data to examine specific dementia subtypes or subclinical vascular brain injury
Differential survival during follow-up by sex may lead to underestimation of dementia risk among men

Abstract

OBJECTIVE: To evaluate the association of early-adulthood and mid-adulthood hypertension with dementia in men and women. METHODS: We evaluated 5,646 members of a diverse integrated health care delivery system who had clinical examinations and health survey data from 1964 to 1973 (mean age 32.7 years; early adulthood) and 1978-1985 (mean age 44.3 years; mid-adulthood) and were members as of January 1, 1996 (mean age 59.8 years). Hypertension categories based on measurements of blood pressure (BP) and change in hypertension categories between the 2 examinations (e.g., onset hypertension) were used to predict dementia incidence from January 1, 1996, to September 30, 2015. Cox proportional hazard models were adjusted for demographics, vascular comorbidities, and hypertension treatment; inverse probability weighting accounted for differential attrition between first BP measurement and start of follow-up. RESULTS: A total of 532 individuals (9.4%) were diagnosed with dementia. Early adulthood hypertension was not associated with dementia, though effect estimates were elevated among women. Mid-adulthood hypertension was associated with 65% (95% confidence interval CI 1.25-2.18) increased dementia risk among women but not men. Onset of hypertension in mid-adulthood predicted 73% higher dementia risk in women (95% CI 1.24-2.40) compared to stable normotensive. There was no evidence that hypertension or changes in hypertension increased dementia risk among men. CONCLUSIONS: Though midlife hypertension was more common in men, it was only associated with dementia risk in women. Sex differences in the timing of dementia risk factors have important implications for brain health and hypertension management.

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