Dementia Risk With Combined Statin and Antihypertensive Drugs That Increase Versus Decrease Angiotensin-II Formation:...

Area of Science:

• Cardiovascular Medicine
• Neurology
• Pharmacology

Background:

• Hypertension and dyslipidaemia are significant modifiable dementia risk factors.
• Combined statin and antihypertensive medication (AHM) use may offer neuroprotection.
• Limited evidence exists on specific AHM-statin combination benefits.

Purpose of the Study:

• To investigate dementia risk associated with statin use combined with Ang-II promoting versus Ang-II suppressing AHMs.
• To compare the efficacy of different AHM classes when used with statins.
• To identify specific statin-AHM combinations with potential cognitive benefits.

Main Methods:

• Prospective cohort study using the 45 and Up Study data (New South Wales, Australia).
• Included participants (≥45 years) with hypertension and dyslipidaemia on concurrent statin and AHM therapy.
• Defined exposure groups: statins + Ang-II promoting AHMs (ARBs, thiazides, DHP CCBs) vs. statins + Ang-II suppressing AHMs (ACEIs, BBs, non-DHP CCBs).
• Used 1:1 propensity score matching and Cox proportional hazards models for analysis.

Main Results:

• Statin plus Ang-II promoting AHM use was linked to a 12% lower dementia risk (HR 0.88) and 13% lower mortality (HR 0.87).
• Rosuvastatin or atorvastatin combined with Ang-II promoting AHMs showed greater risk reduction than simvastatin combinations.
• Protective effects were observed in the 65-74 age group, with ARBs demonstrating superior benefit over ACEIs.

Conclusions:

• Statin plus Ang-II promoting AHM therapy, especially with rosuvastatin or atorvastatin and an ARB, is associated with reduced dementia risk.
• These findings suggest potential cognitive benefits that may guide AHM therapy selection.
• Further randomized trials are recommended to confirm results and elucidate mechanisms.