Long-Term Incidence of Stroke and Dementia in ASCOT

Abstract

Background and purpose: Management of stroke risk factors might reduce later dementia. In ASCOT (Anglo-Scandinavian Outcome Trial), we determined whether dementia or stroke were associated with different blood pressure (BP)–lowering regimens; atorvastatin or placebo; and mean BP, BP variability, and mean cholesterol levels.

Methods: Participants with hypertension and ≥3 cardiovascular disease risk factors were randomly allocated to amlodipine- or atenolol-based BP-lowering regimen targeting BP <140/90 mm Hg for 5.5 years. Participants with total cholesterol ≤6.5 mmol/L were also randomly allocated to atorvastatin 10 mg or placebo for 3.3 years. Mean and LDL (low-density lipoprotein) cholesterol, BP, and SD of BP were calculated from 6 months to end of trial. UK participants were linked to electronic health records to ascertain deaths and hospitalization in general and mental health hospitals. Dementia and stroke were ascertained by validated code lists and within-trial ascertainment.

Results: Of 8580 UK participants, 7300 were followed up to 21 years from randomization. Atorvastatin for 3.3 years had no measurable effect on stroke (264 versus 272; adjusted hazard ratio [HR], 0.92 [95% CI, 0.78–1.09]; P=0.341) or dementia (238 versus 227; adjusted HR, 0.98 [95% CI, 0.82–1.18]; P=0.837) compared with placebo. Mean total cholesterol was not associated with later stroke or dementia. An amlodipine-based compared with an atenolol-based regimen for 5.5 years reduced stroke (443 versus 522; adjusted HR, 0.82 [95% CI, 0.72–0.93]; P=0.003) but not dementia (450 versus 465; adjusted HR, 0.94 [95% CI, 0.82–1.07]; P=0.334) over follow-up. BP variability (SD mean BP) was associated with a higher risk of dementia (per 5 mm Hg HR, 1.14 [95% CI, 1.06–1.24]; P<0.001) and stroke (HR, 1.21 [95% CI, 1.12–1.32]; P<0.001) adjusted for mean BP.

Conclusions: An amlodipine-based BP regimen reduced the long-term incidence of stroke compared with an atenolol-based regimen but had no measurable effect on dementia. Atorvastatin had no effect on either stroke or dementia. Higher BP variability was associated with a higher incidence of later dementia and stroke.

Keywords: blood pressure; cholesterol; dementia; risk factors; stroke.

Figure 1.

Consolidated Standards of Reporting Trials diagram. ASCOT BPLA indicates Anglo-Scandinavian Outcome Trial–Blood Pressure Lowering Arm; ASCOT LLA, Anglo-Scandinavian Outcome Trial–Lipid-Lowering Arm; and EHR, electronic health record.

Figure 2.

Effect of allocation to atorvastatin or placebo in incidence of types of stroke and dementia. A, Stroke; (B) dementia. HR indicates hazard ratio. *Per 1000 person-years. **Adjusted for baseline age, sex, systolic blood pressure, total cholesterol, body mass index, diabetes status, smoking habit, ethnicity, age left full-time education, and blood pressure lowering trial treatment allocation. ***Recorded intracerebral hemorrhage or subarachnoid hemorrhage. TIA indicates transient ischemic attack.

Figure 3.

Effect of allocation to amlodipine-based or atenolol-based regimen blood pressure (BP) lowering on incidence of (A) types and subtypes of stroke and (B) dementia. HR indicates hazard ratio. *Per 1000 person-years. **Adjusted for baseline age, sex, systolic BP, total cholesterol, body mass index, diabetes status, smoking habit, ethnicity, age left full-time education, and blood pressure lowering trial treatment allocation. ***Recorded intracerebral hemorrhage or subarachnoid hemorrhage.