Association of orthostatic hypotension with incident dementia, stroke, and cognitive decline

Abstract

Objective: To examine associations of orthostatic hypotension (OH) with dementia and long-term cognitive decline and to update previously published results in the same cohort for stroke with an additional 16 years of follow-up.

Methods: We analyzed data from 11,709 participants without a history of coronary heart disease or stroke who attended the baseline examination (1987-1989) of the prospective Atherosclerosis Risk in Communities (ARIC) study. OH was defined as a drop in systolic blood pressure (BP) of at least 20 mm Hg or a drop in diastolic BP of at least 10 mm Hg on standing. Dementia was ascertained via examination, contact with participants or their proxy, or medical record surveillance. Ischemic stroke was ascertained via cohort surveillance of hospitalizations, cohort follow-up, and linkage with registries. Both outcomes were adjudicated. Cognitive function was ascertained via 3 neuropsychological tests administered in 1990 to 1992 and 1996 to 1998 and a full battery of tests in 2011 to 2013. Scores were summarized and reported as SDs. We used adjusted Cox regression and linear mixed models.

Results: Over ≈25 years, 1,068 participants developed dementia and 842 had an ischemic stroke. Compared to persons without OH at baseline, those with OH had a higher risk of dementia (hazard ratio [HR] 1.54, 95% confidence interval [CI] 1.20-1.97) and ischemic stroke (HR 2.08, 95% CI 1.65-2.62). Persons with OH had greater, although nonsignificant, cognitive decline over 20 years (SD 0.09, 95% CI -0.02 to 0.21).

Conclusions: OH assessed in midlife was independently associated with incident dementia and ischemic stroke. Additional studies are needed to elucidate potential mechanisms for these associations and possible applications for prevention.

Figure 1. HR (95% CI) for Incident ischemic stroke and incident dementia by change in SBP and DBP from supine to standing

(A) Incident dementia. (B) Incident stroke. Hazard ratios (HRs) (95% confidence intervals [CIs]) are from Cox proportional hazards regression with adjustment for age, race, sex, education, smoking status (current, former, never), drinking status (current, former, never), body mass index, diabetes mellitus (yes/no), glucose, APOE ε4 (presence of ε4 allele, 0 or ≥1 alleles), high-density lipoprotein cholesterol, and total cholesterol. Change in systolic (SBP) and diastolic (DBP) blood pressure from supine to standing was modeled with restricted cubic splines with knots at the 10th, 50th, and 90th percentiles. These correspond to z scores of −1.225, −0.05, and 1.17. All graphs truncated at ±4 SDs for SBP and DBP. Change in BP is calculated as mean standing BP (excluding the first standing measurement) minus mean supine BP.

Figure 2. HRs (95% CIs) for (A) incident dementia and (B) incident ischemic stroke in persons with OH compared to those without, stratified by hypertension, diabetes mellitus, race, and APOE ε4

Hazard ratios (HRs) (95% confidence intervals [CIs]) are from stratified Cox proportional hazards regression with adjustment for age, sex, education, smoking status (current, former, never), drinking status (current, former, never), body mass index, glucose, APOE ε4 (presence of ε4 allele, 0 or ≥1 alleles), high-density lipoprotein cholesterol, total cholesterol, and, as applicable, hypertension, diabetes mellitus, and race. To calculate p values for interaction, we fit Cox models that included all categories (of hypertension, diabetes mellitus, race, or APOE ε4) with an interaction term between the categories and orthostatic hypotension (OH). The p values for interaction are from χ² tests that test the interaction terms that are not significantly different from 1.